G-quadruplex (G4)-driven epigenomic aging - Revision history

Dmitry Dzhagarov: /* Small molecules targeting G4 */

2024-08-07T15:03:28Z

Small molecules targeting G4

← Older revision		Revision as of 15:03, 7 August 2024
Line 28:		Line 28:
	<ref>Zhang, X., Spiegel, J., Martinez Cuesta, S., Adhikari, S. & Balasubramanian, S. (2021). Chemical profiling of DNA G-quadruplex-interacting proteins in live cells. Nat Chem 13, 626-633</ref>		<ref>Zhang, X., Spiegel, J., Martinez Cuesta, S., Adhikari, S. & Balasubramanian, S. (2021). Chemical profiling of DNA G-quadruplex-interacting proteins in live cells. Nat Chem 13, 626-633</ref>
	<ref>Sergeev, A. V., Loiko, A. G., Genatullina, A. I., Petrov, A. S., Kubareva, E. A., Dolinnaya, N. G., & Gromova, E. S. (2023). Crosstalk between G-Quadruplexes and Dnmt3a-Mediated Methylation of the c-MYC Oncogene Promoter. International Journal of Molecular Sciences, 25(1), 45. https://doi.org/10.3390/ijms25010045</ref>		<ref>Sergeev, A. V., Loiko, A. G., Genatullina, A. I., Petrov, A. S., Kubareva, E. A., Dolinnaya, N. G., & Gromova, E. S. (2023). Crosstalk between G-Quadruplexes and Dnmt3a-Mediated Methylation of the c-MYC Oncogene Promoter. International Journal of Molecular Sciences, 25(1), 45. https://doi.org/10.3390/ijms25010045</ref>
			<ref>Soriano-Lerma, A., Sanchez-Martin, V., Murciano-Calles, J., Ortiz-Gonzalez, M., Tello-Lopez, M. J., Perez-Carrasco, V., ... & Garcia-Salcedo, J. A. (2024). Resveratrol targets G-quadruplexes to exert its pharmacological effects. bioRxiv, 2024-07. https://doi.org/10.1101/2024.07.29.605564</ref>

	== G4 may participate in non-genetic mechanisms driving aging ==		== G4 may participate in non-genetic mechanisms driving aging ==

Dmitry Dzhagarov: /* Small molecules targeting G4 */

2024-07-13T07:02:12Z

Small molecules targeting G4

← Older revision		Revision as of 07:02, 13 July 2024
Line 13:		Line 13:

	== Small molecules targeting G4 ==		== Small molecules targeting G4 ==
	Small molecules targeting G-quadruplexes are also important as potent drugs for therapy of cancer and other diseases.<ref>Cao, S., Su, Q., Chen, Y. H., Wang, M. L., Xu, Y., Wang, L. H., ... & Wang, Z. G. (2024). Molecular Insights into the Specific Targeting of c-MYC G-Quadruplex by Thiazole Peptides. International Journal of Molecular Sciences, 25(1), 623. https://doi.org/10.3390/ijms25010623</ref><ref>Monsen, R.C. (2023). Higher-order G-quadruplexes in promoters are untapped drug targets. Front. Chem., 11, 1211512.</ref><ref>Wang, K.B.; Elsayed, M.S.A.; Wu, G.; et al. (2019). Indenoisoquinoline Topoisomerase Inhibitors Strongly Bind and Stabilize the MYC Promoter G-Quadruplex and Downregulate MYC. J. Am. Chem. Soc., 141, 11059–11070.</ref><ref>Shu, H.; Zhang, R.; Xiao, K.; et al. (2022). G-Quadruplex-Binding Proteins: Promising Targets for Drug Design. Biomolecules, 12, 648.</ref><ref>Kosiol, N.; Juranek, S.; Brossart, P.; et al. (2021). G-quadruplexes: A promising target for cancer therapy. Mol. Cancer, 20, 40.</ref><ref>Teng, F.Y.; Jiang, Z.Z.; Guo, M.; et al. (2021). G-quadruplex DNA: A novel target for drug design. Cell. Mol. Life Sci., 78, 6557–6583.</ref><ref>Zou, M.; Li, J.Y.; Zhang, M.J.; et al. (2021). G-quadruplex binder pyridostatin as an effective multi-target ZIKV inhibitor. Int. J. Biol. Macromol., 190, 178–188.</ref><ref>Hu, X.X.; Wang, S.Q.; Gan, S.Q.; et al. (2021). A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation. Front. Chem., 9, 781198.</ref><ref>Miglietta, G.; Marinello, J.; Russo, M.; Capranico, G. (2019). Ligands stimulating antitumour immunity as the next G-quadruplex challenge. Mol. Cancer 2022, 21, 180.</ref><ref>Dhamodharan, V.; Pradeepkumar, P.I. Specific Recognition of Promoter G-Quadruplex DNAs by Small Molecule Ligands and Light-up Probes. ACS Chem. Biol., 14, 2102–2114.</ref><ref>Yang, D.; Okamoto, K. (2010). Structural Insights into G-Quadruplexes: Towards New Anticancer Drugs. Future Med. Chem., 2, 619–646.</ref><ref>Neidle, S.; Parkinson, G. (2002). Telomere Maintenance as a Target for Anticancer Drug Discovery. Nat. Rev. Drug Discov., 1, 383–393. </ref><ref>Sun, D.; Thompson, B.; Cathers, B.E. et al. (1997). Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound. J. Med. Chem., 40, 2113–2116.</ref>		Small molecules targeting G-quadruplexes are also important as potent drugs for therapy of cancer and other diseases.<ref>Cao, S., Su, Q., Chen, Y. H., Wang, M. L., Xu, Y., Wang, L. H., ... & Wang, Z. G. (2024). Molecular Insights into the Specific Targeting of c-MYC G-Quadruplex by Thiazole Peptides. International Journal of Molecular Sciences, 25(1), 623. https://doi.org/10.3390/ijms25010623</ref><ref>Monsen, R.C. (2023). Higher-order G-quadruplexes in promoters are untapped drug targets. Front. Chem., 11, 1211512.</ref><ref>Wang, K.B.; Elsayed, M.S.A.; Wu, G.; et al. (2019). Indenoisoquinoline Topoisomerase Inhibitors Strongly Bind and Stabilize the MYC Promoter G-Quadruplex and Downregulate MYC. J. Am. Chem. Soc., 141, 11059–11070.</ref><ref>Shu, H.; Zhang, R.; Xiao, K.; et al. (2022). G-Quadruplex-Binding Proteins: Promising Targets for Drug Design. Biomolecules, 12, 648.</ref><ref>Kosiol, N.; Juranek, S.; Brossart, P.; et al. (2021). G-quadruplexes: A promising target for cancer therapy. Mol. Cancer, 20, 40.</ref><ref>Teng, F.Y.; Jiang, Z.Z.; Guo, M.; et al. (2021). G-quadruplex DNA: A novel target for drug design. Cell. Mol. Life Sci., 78, 6557–6583.</ref><ref>Zou, M.; Li, J.Y.; Zhang, M.J.; et al. (2021). G-quadruplex binder pyridostatin as an effective multi-target ZIKV inhibitor. Int. J. Biol. Macromol., 190, 178–188.</ref><ref>Hu, X.X.; Wang, S.Q.; Gan, S.Q.; et al. (2021). A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation. Front. Chem., 9, 781198.</ref><ref>Miglietta, G.; Marinello, J.; Russo, M.; Capranico, G. (2019). Ligands stimulating antitumour immunity as the next G-quadruplex challenge. Mol. Cancer 2022, 21, 180.</ref><ref>Dhamodharan, V.; Pradeepkumar, P.I. Specific Recognition of Promoter G-Quadruplex DNAs by Small Molecule Ligands and Light-up Probes. ACS Chem. Biol., 14, 2102–2114.</ref><ref>Yang, D.; Okamoto, K. (2010). Structural Insights into G-Quadruplexes: Towards New Anticancer Drugs. Future Med. Chem., 2, 619–646.</ref><ref>Neidle, S.; Parkinson, G. (2002). Telomere Maintenance as a Target for Anticancer Drug Discovery. Nat. Rev. Drug Discov., 1, 383–393. </ref><ref>Sun, D.; Thompson, B.; Cathers, B.E. et al. (1997). Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound. J. Med. Chem., 40, 2113–2116.</ref><ref>Merlino, F., Marzano, S., Zizza, P., D’Aria, F., Grasso, N., Carachino, A., ... & Pagano, B. (2024). Unlocking the potential of protein-derived peptides to target G-quadruplex DNA: from recognition to anticancer activity. Nucleic Acids Research, 52(12), 6748–6762, https://doi.org/10.1093/nar/gkae471</ref>

Dmitry Dzhagarov: /* Small molecules targeting G4 */

2024-01-12T18:41:29Z

Small molecules targeting G4

← Older revision		Revision as of 18:41, 12 January 2024
Line 13:		Line 13:

	== Small molecules targeting G4 ==		== Small molecules targeting G4 ==
	Small molecules targeting G-quadruplexes are also important as potent drugs for therapy of cancer and other diseases.<ref>Monsen, R.C. (2023). Higher-order G-quadruplexes in promoters are untapped drug targets. Front. Chem., 11, 1211512.</ref><ref>Wang, K.B.; Elsayed, M.S.A.; Wu, G.; et al. (2019). Indenoisoquinoline Topoisomerase Inhibitors Strongly Bind and Stabilize the MYC Promoter G-Quadruplex and Downregulate MYC. J. Am. Chem. Soc., 141, 11059–11070.</ref><ref>Shu, H.; Zhang, R.; Xiao, K.; et al. (2022). G-Quadruplex-Binding Proteins: Promising Targets for Drug Design. Biomolecules, 12, 648.</ref><ref>Kosiol, N.; Juranek, S.; Brossart, P.; et al. (2021). G-quadruplexes: A promising target for cancer therapy. Mol. Cancer, 20, 40.</ref><ref>Teng, F.Y.; Jiang, Z.Z.; Guo, M.; et al. (2021). G-quadruplex DNA: A novel target for drug design. Cell. Mol. Life Sci., 78, 6557–6583.</ref><ref>Zou, M.; Li, J.Y.; Zhang, M.J.; et al. (2021). G-quadruplex binder pyridostatin as an effective multi-target ZIKV inhibitor. Int. J. Biol. Macromol., 190, 178–188.</ref><ref>Hu, X.X.; Wang, S.Q.; Gan, S.Q.; et al. (2021). A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation. Front. Chem., 9, 781198.</ref><ref>Miglietta, G.; Marinello, J.; Russo, M.; Capranico, G. (2019). Ligands stimulating antitumour immunity as the next G-quadruplex challenge. Mol. Cancer 2022, 21, 180.</ref><ref>Dhamodharan, V.; Pradeepkumar, P.I. Specific Recognition of Promoter G-Quadruplex DNAs by Small Molecule Ligands and Light-up Probes. ACS Chem. Biol., 14, 2102–2114.</ref><ref>Yang, D.; Okamoto, K. (2010). Structural Insights into G-Quadruplexes: Towards New Anticancer Drugs. Future Med. Chem., 2, 619–646.</ref><ref>Neidle, S.; Parkinson, G. (2002). Telomere Maintenance as a Target for Anticancer Drug Discovery. Nat. Rev. Drug Discov., 1, 383–393. </ref><ref>Sun, D.; Thompson, B.; Cathers, B.E. et al. (1997). Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound. J. Med. Chem., 40, 2113–2116.</ref>		Small molecules targeting G-quadruplexes are also important as potent drugs for therapy of cancer and other diseases.<ref>Cao, S., Su, Q., Chen, Y. H., Wang, M. L., Xu, Y., Wang, L. H., ... & Wang, Z. G. (2024). Molecular Insights into the Specific Targeting of c-MYC G-Quadruplex by Thiazole Peptides. International Journal of Molecular Sciences, 25(1), 623. https://doi.org/10.3390/ijms25010623</ref><ref>Monsen, R.C. (2023). Higher-order G-quadruplexes in promoters are untapped drug targets. Front. Chem., 11, 1211512.</ref><ref>Wang, K.B.; Elsayed, M.S.A.; Wu, G.; et al. (2019). Indenoisoquinoline Topoisomerase Inhibitors Strongly Bind and Stabilize the MYC Promoter G-Quadruplex and Downregulate MYC. J. Am. Chem. Soc., 141, 11059–11070.</ref><ref>Shu, H.; Zhang, R.; Xiao, K.; et al. (2022). G-Quadruplex-Binding Proteins: Promising Targets for Drug Design. Biomolecules, 12, 648.</ref><ref>Kosiol, N.; Juranek, S.; Brossart, P.; et al. (2021). G-quadruplexes: A promising target for cancer therapy. Mol. Cancer, 20, 40.</ref><ref>Teng, F.Y.; Jiang, Z.Z.; Guo, M.; et al. (2021). G-quadruplex DNA: A novel target for drug design. Cell. Mol. Life Sci., 78, 6557–6583.</ref><ref>Zou, M.; Li, J.Y.; Zhang, M.J.; et al. (2021). G-quadruplex binder pyridostatin as an effective multi-target ZIKV inhibitor. Int. J. Biol. Macromol., 190, 178–188.</ref><ref>Hu, X.X.; Wang, S.Q.; Gan, S.Q.; et al. (2021). A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation. Front. Chem., 9, 781198.</ref><ref>Miglietta, G.; Marinello, J.; Russo, M.; Capranico, G. (2019). Ligands stimulating antitumour immunity as the next G-quadruplex challenge. Mol. Cancer 2022, 21, 180.</ref><ref>Dhamodharan, V.; Pradeepkumar, P.I. Specific Recognition of Promoter G-Quadruplex DNAs by Small Molecule Ligands and Light-up Probes. ACS Chem. Biol., 14, 2102–2114.</ref><ref>Yang, D.; Okamoto, K. (2010). Structural Insights into G-Quadruplexes: Towards New Anticancer Drugs. Future Med. Chem., 2, 619–646.</ref><ref>Neidle, S.; Parkinson, G. (2002). Telomere Maintenance as a Target for Anticancer Drug Discovery. Nat. Rev. Drug Discov., 1, 383–393. </ref><ref>Sun, D.; Thompson, B.; Cathers, B.E. et al. (1997). Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound. J. Med. Chem., 40, 2113–2116.</ref>

Dmitry Dzhagarov: /* G4 may participate in non-genetic mechanisms driving aging */

2024-01-12T18:34:13Z

G4 may participate in non-genetic mechanisms driving aging

← Older revision		Revision as of 18:34, 12 January 2024
Line 30:		Line 30:

	== G4 may participate in non-genetic mechanisms driving aging ==		== G4 may participate in non-genetic mechanisms driving aging ==
			G4s accumulate at specific genomic loci during aging and the coefficient of variation of the G4 signal increased with cell age.<ref name="universal" >Jin, W., Zheng, J., Xiao, Y., Ju, L., Chen, F., Fu, J., ... & Zhang, Y. (2024). A universal molecular mechanism driving aging. bioRxiv, 2024-01. https://doi.org/10.1101/2024.01.06.574476</ref> This G4 accumulation drives clock-like chromatin opening, since G4 formation drives aging-associated, clock like chromatin opening.<ref name="universal" />
	<ref>Jin, W., Zheng, J., Xiao, Y., Ju, L., Chen, F., Fu, J., ... & Zhang, Y. (2024). A universal molecular mechanism driving aging. bioRxiv, 2024-01. https://doi.org/10.1101/2024.01.06.574476</ref>		It was shown that delayed genome replication is a general feature of aging loci and that G4 stimulates local transcription replication interaction to delay genome replication.<ref name="universal" /> The authors of the article also hypothesized that G4 stability might also regulate age-associated DNA hypomethylation.<ref name="universal" /> The authors also suggest that "perturbing G4 formation might be of particular interest for modulating natural and pathological aging".<ref name="universal" />
			== References ==
			<references />

			[[Category:Main list]]
	[[Category:Drafts]]		[[Category:Drafts]]

Dmitry Dzhagarov: /* Small molecules targeting G4 */

2024-01-12T17:47:08Z

Small molecules targeting G4

← Older revision		Revision as of 17:47, 12 January 2024
Line 27:		Line 27:
	<ref>Muller, S., Kumari, S., Rodriguez, R. & Balasubramanian, S. (2010). Small-molecule-mediated G768 quadruplex isolation from human cells. Nat Chem 2, 1095-1098</ref>		<ref>Muller, S., Kumari, S., Rodriguez, R. & Balasubramanian, S. (2010). Small-molecule-mediated G768 quadruplex isolation from human cells. Nat Chem 2, 1095-1098</ref>
	<ref>Zhang, X., Spiegel, J., Martinez Cuesta, S., Adhikari, S. & Balasubramanian, S. (2021). Chemical profiling of DNA G-quadruplex-interacting proteins in live cells. Nat Chem 13, 626-633</ref>		<ref>Zhang, X., Spiegel, J., Martinez Cuesta, S., Adhikari, S. & Balasubramanian, S. (2021). Chemical profiling of DNA G-quadruplex-interacting proteins in live cells. Nat Chem 13, 626-633</ref>
			<ref>Sergeev, A. V., Loiko, A. G., Genatullina, A. I., Petrov, A. S., Kubareva, E. A., Dolinnaya, N. G., & Gromova, E. S. (2023). Crosstalk between G-Quadruplexes and Dnmt3a-Mediated Methylation of the c-MYC Oncogene Promoter. International Journal of Molecular Sciences, 25(1), 45. https://doi.org/10.3390/ijms25010045</ref>

	== G4 may participate in non-genetic mechanisms driving aging ==		== G4 may participate in non-genetic mechanisms driving aging ==

Dmitry Dzhagarov at 16:52, 11 January 2024

2024-01-11T16:52:49Z

← Older revision		Revision as of 16:52, 11 January 2024
Line 1:		Line 1:
	Nucleic acid sequences rich in guanine are capable of forming '''four-stranded structures called G-quadruplexes(G4)''', stabilized by hydrogen bonding between a tetrad of guanine bases<ref>Sen D, Gilbert W (1988). Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228</ref> and it generally extends over the C-rich strand forming a 3′ overhang reaching approximately 50–300 nucleotides in mammals.<ref>Chai, W., Du, Q., Shay, J. W., & Wright, W. E. (2006). Human telomeres have different overhang sizes at leading versus lagging strands. Molecular cell, 21(3), 427-435. PMID: 16455497 DOI: 10.1016/j.molcel.2005.12.004</ref> Endogenous G4 (eG4), with its unique secondary structure, is involved in a variety of important biological processes such as gene transcription, translation regulation, telomere extension, and chromatin modification. <ref name="In vivo" >Zhang, Z. H., Qian, S. H., Wei, D., & Chen, Z. X. (2023). In vivo dynamics and regulation of DNA G-quadruplex structures in mammals. Cell & Bioscience, 13(1), 117. PMID: 37381029 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303365 PMC10303365] DOI: 10.1186/s13578-023-01074-8</ref>		Nucleic acid sequences rich in guanine are capable of forming '''four-stranded structures called G-quadruplexes(G4)''', stabilized by hydrogen bonding between a tetrad of guanine bases<ref>Sen D, Gilbert W (1988). Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228</ref> and it generally extends over the C-rich strand forming a 3′ overhang reaching approximately 50–300 nucleotides in mammals.<ref>Chai, W., Du, Q., Shay, J. W., & Wright, W. E. (2006). Human telomeres have different overhang sizes at leading versus lagging strands. Molecular cell, 21(3), 427-435. PMID: 16455497 DOI: 10.1016/j.molcel.2005.12.004</ref> Endogenous G4 (eG4), with its unique secondary structure, is involved in a variety of important biological processes such as gene transcription, translation regulation, telomere extension, and chromatin modification. <ref name="In vivo" >Zhang, Z. H., Qian, S. H., Wei, D., & Chen, Z. X. (2023). In vivo dynamics and regulation of DNA G-quadruplex structures in mammals. Cell & Bioscience, 13(1), 117. PMID: 37381029 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303365 PMC10303365] DOI: 10.1186/s13578-023-01074-8</ref>

	The structures of eG4s are affected by interacting proteins in vivo. During DNA replication, dsDNA is unwound into ssDNA by helicases and stabilized by ssDNA-binding proteins. During transcription, the promoter TATA box interacts with TFIIH to melt the promoter. As a kind of nucleic acid structures, eG4s will inevitably be regulated by interacting proteins. The proteins that can interact with eG4s can be divided into two types according to their functions: one is the protein that can unfold eG4s (such as G4 helicase), and the other is the protein that can bind and stabilize eG4s. These two types of proteins together regulate the dynamics of eG4s in vivo.<ref name="In vivo" />		The structures of eG4s are affected by interacting proteins in vivo. During DNA replication, double-stranded (dsDNA) is unwound into single-stranded DNA (ssDNA) by helicases<ref>Mendoza, O., Bourdoncle, A., Boulé, J. B., Brosh Jr, R. M., & Mergny, J. L. (2016). G-quadruplexes and helicases. Nucleic acids research, 44(5), 1989-2006.</ref> and stabilized by ssDNA-binding proteins. During transcription, the promoter TATA box interacts with TFIIH to melt the promoter. As a kind of nucleic acid structures, eG4s will inevitably be regulated by interacting proteins. The proteins that can interact with eG4s can be divided into two types according to their functions: one is the protein that can unfold eG4s (such as G4 helicase), and the other is the protein that can bind and stabilize eG4s. These two types of proteins together regulate the dynamics of eG4s in vivo.<ref name="In vivo" />

	Transcription of the C-rich telomeric strand generates a class of telomeric repeat-containing RNAs called TERRA (TElomere Repeat-containing RNA) with distinct subtelomeric sequences at their 5′ end and '''the same G-rich telomeric sequence at their 3′ end'''. These features are shared by TERRA molecules expressed by all the organisms studied to date.<ref>Barral, A., & Déjardin, J. (2020). Telomeric chromatin and TERRA. Journal of molecular biology, 432(15), 4244-4256. PMID: 32151584 DOI: 10.1016/j.jmb.2020.03.003</ref> Recent evidence indicates that aging is a condition which results in upregulation of TERRA in different cellular settings.<ref>Rivosecchi, J., & Cusanelli, E. (2023). TERRA beyond cancer: the biology of telomeric repeat‐containing RNAs in somatic and germ cells. Frontiers in Aging, 4. PMID: 37636218 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448526/ PMC10448526] DOI: 10.3389/fragi.2023.1224225</ref><ref>Canale, P., Campolo, J., Borghini, A., & Andreassi, M. G. (2023). Long Telomeric Repeat-Containing RNA (TERRA): Biological Functions and Challenges in Vascular Aging and Disease. Biomedicines, 11(12), 3211. PMID: 38137431 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740775/ PMC10740775] DOI: 10.3390/biomedicines11123211</ref> The G-quadruplex structure of TERRA is an important recognition element for the TRF2 shelterin subunit and physically interacts with it to bind to telomeric DNA and also with TRF1 to preserve the telomere’s structural stability.<ref>Abreu, P. L., Lee, Y. W., & Azzalin, C. M. (2022). In Vitro Characterization of the Physical Interactions between the Long Noncoding RNA TERRA and the Telomeric Proteins TRF1 and TRF2. International Journal of Molecular Sciences, 23(18), 10463. PMID: 36142374 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500956 PMC9500956] DOI: 10.3390/ijms231810463</ref><ref>Rivosecchi, J., Jurikova, K., & Cusanelli, E. (2024). Telomere-specific regulation of TERRA and its impact on telomere stability. In Seminars in Cell & Developmental Biology (Vol. 157, pp. 3-23). Academic Press.</ref>		Transcription of the C-rich telomeric strand generates a class of telomeric repeat-containing RNAs called TERRA (TElomere Repeat-containing RNA) with distinct subtelomeric sequences at their 5′ end and '''the same G-rich telomeric sequence at their 3′ end'''. These features are shared by TERRA molecules expressed by all the organisms studied to date.<ref>Barral, A., & Déjardin, J. (2020). Telomeric chromatin and TERRA. Journal of molecular biology, 432(15), 4244-4256. PMID: 32151584 DOI: 10.1016/j.jmb.2020.03.003</ref> Recent evidence indicates that aging is a condition which results in upregulation of TERRA in different cellular settings.<ref>Rivosecchi, J., & Cusanelli, E. (2023). TERRA beyond cancer: the biology of telomeric repeat‐containing RNAs in somatic and germ cells. Frontiers in Aging, 4. PMID: 37636218 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448526/ PMC10448526] DOI: 10.3389/fragi.2023.1224225</ref><ref>Canale, P., Campolo, J., Borghini, A., & Andreassi, M. G. (2023). Long Telomeric Repeat-Containing RNA (TERRA): Biological Functions and Challenges in Vascular Aging and Disease. Biomedicines, 11(12), 3211. PMID: 38137431 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740775/ PMC10740775] DOI: 10.3390/biomedicines11123211</ref> The G-quadruplex structure of TERRA is an important recognition element for the TRF2 shelterin subunit and physically interacts with it to bind to telomeric DNA and also with TRF1 to preserve the telomere’s structural stability.<ref>Abreu, P. L., Lee, Y. W., & Azzalin, C. M. (2022). In Vitro Characterization of the Physical Interactions between the Long Noncoding RNA TERRA and the Telomeric Proteins TRF1 and TRF2. International Journal of Molecular Sciences, 23(18), 10463. PMID: 36142374 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500956 PMC9500956] DOI: 10.3390/ijms231810463</ref><ref>Rivosecchi, J., Jurikova, K., & Cusanelli, E. (2024). Telomere-specific regulation of TERRA and its impact on telomere stability. In Seminars in Cell & Developmental Biology (Vol. 157, pp. 3-23). Academic Press.</ref>

	The formation of telomeric quadruplexes has been shown to decrease the activity of the enzyme telomerase, which is responsible for elongating telomeres.<ref>Fletcher, T. M., Sun, D., Salazar, M., & Hurley, L. H. (1998). Effect of DNA secondary structure on human telomerase activity. Biochemistry, 37(16), 5536-5541. PMID: 9548937 DOI: 10.1021/bi972681p</ref><ref>Bryan, T. M. (2020). G-quadruplexes at telomeres: friend or foe?. Molecules, 25(16), 3686. PMID: 32823549 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464828/ PMC7464828] DOI: 10.3390/molecules25163686</ref>		The formation of telomeric quadruplexes has been shown to decrease the activity of the enzyme telomerase, which is responsible for elongating telomeres.<ref>De Cian, A., Cristofari, G., Reichenbach, P., De Lemos, E., Monchaud, D., Teulade-Fichou, M. P., ... & Mergny, J. L. (2007). Reevaluation of telomerase inhibition by quadruplex ligands and their mechanisms of action. Proceedings of the National Academy of Sciences, 104(44), 17347-17352.</ref><ref>Fletcher, T. M., Sun, D., Salazar, M., & Hurley, L. H. (1998). Effect of DNA secondary structure on human telomerase activity. Biochemistry, 37(16), 5536-5541. PMID: 9548937 DOI: 10.1021/bi972681p</ref><ref>Bryan, T. M. (2020). G-quadruplexes at telomeres: friend or foe?. Molecules, 25(16), 3686. PMID: 32823549 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464828/ PMC7464828] DOI: 10.3390/molecules25163686</ref>


Line 11:		Line 11:

	High occurrences of oxidized guanines in G4 structures due to the oxidative stress occurring under the influence of the reactive oxygen species (ROS) affects the genome stability and promotes mutagenesis, that can destabilize the stacking of guanin, senescence, and other age-related diseases.<ref>Bielskutė, S., Plavec, J., & Podbevšek, P. (2019). Impact of oxidative lesions on the human telomeric G-quadruplex. Journal of the American Chemical Society, 141(6), 2594-2603. PMID: 30657306 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727377 PMC6727377] DOI: 10.1021/jacs.8b12748</ref><ref>Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., ... & Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical interventions in aging, 757-772. PMID: 29731617 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927356 PMC5927356] DOI: 10.2147/CIA.S158513</ref> G4s in CDS (the coding sequence, that codes for a protein) and CpG regions (that contain several CpG methylated sequences of DNA) are the least likely regions to be affected by mutations, while enhancers and intergenic G4s are prone to higher variant-induced stabilization and destabilization due to the single-nucleotide variants.<ref>Neupane, A., Chariker, J. H., & Rouchka, E. C. (2023). Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states. Genes, 14(12), 2125. PMID: 36778288 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915501 PMC9915501] DOI: 10.1101/2023.01.30.526341</ref>		High occurrences of oxidized guanines in G4 structures due to the oxidative stress occurring under the influence of the reactive oxygen species (ROS) affects the genome stability and promotes mutagenesis, that can destabilize the stacking of guanin, senescence, and other age-related diseases.<ref>Bielskutė, S., Plavec, J., & Podbevšek, P. (2019). Impact of oxidative lesions on the human telomeric G-quadruplex. Journal of the American Chemical Society, 141(6), 2594-2603. PMID: 30657306 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727377 PMC6727377] DOI: 10.1021/jacs.8b12748</ref><ref>Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., ... & Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical interventions in aging, 757-772. PMID: 29731617 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927356 PMC5927356] DOI: 10.2147/CIA.S158513</ref> G4s in CDS (the coding sequence, that codes for a protein) and CpG regions (that contain several CpG methylated sequences of DNA) are the least likely regions to be affected by mutations, while enhancers and intergenic G4s are prone to higher variant-induced stabilization and destabilization due to the single-nucleotide variants.<ref>Neupane, A., Chariker, J. H., & Rouchka, E. C. (2023). Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states. Genes, 14(12), 2125. PMID: 36778288 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915501 PMC9915501] DOI: 10.1101/2023.01.30.526341</ref>

			== Small molecules targeting G4 ==
			Small molecules targeting G-quadruplexes are also important as potent drugs for therapy of cancer and other diseases.<ref>Monsen, R.C. (2023). Higher-order G-quadruplexes in promoters are untapped drug targets. Front. Chem., 11, 1211512.</ref><ref>Wang, K.B.; Elsayed, M.S.A.; Wu, G.; et al. (2019). Indenoisoquinoline Topoisomerase Inhibitors Strongly Bind and Stabilize the MYC Promoter G-Quadruplex and Downregulate MYC. J. Am. Chem. Soc., 141, 11059–11070.</ref><ref>Shu, H.; Zhang, R.; Xiao, K.; et al. (2022). G-Quadruplex-Binding Proteins: Promising Targets for Drug Design. Biomolecules, 12, 648.</ref><ref>Kosiol, N.; Juranek, S.; Brossart, P.; et al. (2021). G-quadruplexes: A promising target for cancer therapy. Mol. Cancer, 20, 40.</ref><ref>Teng, F.Y.; Jiang, Z.Z.; Guo, M.; et al. (2021). G-quadruplex DNA: A novel target for drug design. Cell. Mol. Life Sci., 78, 6557–6583.</ref><ref>Zou, M.; Li, J.Y.; Zhang, M.J.; et al. (2021). G-quadruplex binder pyridostatin as an effective multi-target ZIKV inhibitor. Int. J. Biol. Macromol., 190, 178–188.</ref><ref>Hu, X.X.; Wang, S.Q.; Gan, S.Q.; et al. (2021). A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation. Front. Chem., 9, 781198.</ref><ref>Miglietta, G.; Marinello, J.; Russo, M.; Capranico, G. (2019). Ligands stimulating antitumour immunity as the next G-quadruplex challenge. Mol. Cancer 2022, 21, 180.</ref><ref>Dhamodharan, V.; Pradeepkumar, P.I. Specific Recognition of Promoter G-Quadruplex DNAs by Small Molecule Ligands and Light-up Probes. ACS Chem. Biol., 14, 2102–2114.</ref><ref>Yang, D.; Okamoto, K. (2010). Structural Insights into G-Quadruplexes: Towards New Anticancer Drugs. Future Med. Chem., 2, 619–646.</ref><ref>Neidle, S.; Parkinson, G. (2002). Telomere Maintenance as a Target for Anticancer Drug Discovery. Nat. Rev. Drug Discov., 1, 383–393. </ref><ref>Sun, D.; Thompson, B.; Cathers, B.E. et al. (1997). Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound. J. Med. Chem., 40, 2113–2116.</ref>


Line 24:		Line 27:
	<ref>Muller, S., Kumari, S., Rodriguez, R. & Balasubramanian, S. (2010). Small-molecule-mediated G768 quadruplex isolation from human cells. Nat Chem 2, 1095-1098</ref>		<ref>Muller, S., Kumari, S., Rodriguez, R. & Balasubramanian, S. (2010). Small-molecule-mediated G768 quadruplex isolation from human cells. Nat Chem 2, 1095-1098</ref>
	<ref>Zhang, X., Spiegel, J., Martinez Cuesta, S., Adhikari, S. & Balasubramanian, S. (2021). Chemical profiling of DNA G-quadruplex-interacting proteins in live cells. Nat Chem 13, 626-633</ref>		<ref>Zhang, X., Spiegel, J., Martinez Cuesta, S., Adhikari, S. & Balasubramanian, S. (2021). Chemical profiling of DNA G-quadruplex-interacting proteins in live cells. Nat Chem 13, 626-633</ref>

			== G4 may participate in non-genetic mechanisms driving aging ==

	<ref>Jin, W., Zheng, J., Xiao, Y., Ju, L., Chen, F., Fu, J., ... & Zhang, Y. (2024). A universal molecular mechanism driving aging. bioRxiv, 2024-01. https://doi.org/10.1101/2024.01.06.574476</ref>		<ref>Jin, W., Zheng, J., Xiao, Y., Ju, L., Chen, F., Fu, J., ... & Zhang, Y. (2024). A universal molecular mechanism driving aging. bioRxiv, 2024-01. https://doi.org/10.1101/2024.01.06.574476</ref>

Dmitry Dzhagarov at 14:13, 11 January 2024

2024-01-11T14:13:08Z

← Older revision		Revision as of 14:13, 11 January 2024
Line 1:		Line 1:
	Nucleic acid sequences rich in guanine are capable of forming '''four-stranded structures called G-quadruplexes(G4)''', stabilized by hydrogen bonding between a tetrad of guanine bases<ref>Sen D, Gilbert W (1988). Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228</ref> and it generally extends over the C-rich strand forming a 3′ overhang reaching approximately 50–300 nucleotides in mammals.<ref>Chai, W., Du, Q., Shay, J. W., & Wright, W. E. (2006). Human telomeres have different overhang sizes at leading versus lagging strands. Molecular cell, 21(3), 427-435. PMID: 16455497 DOI: 10.1016/j.molcel.2005.12.004</ref>		Nucleic acid sequences rich in guanine are capable of forming '''four-stranded structures called G-quadruplexes(G4)''', stabilized by hydrogen bonding between a tetrad of guanine bases<ref>Sen D, Gilbert W (1988). Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228</ref> and it generally extends over the C-rich strand forming a 3′ overhang reaching approximately 50–300 nucleotides in mammals.<ref>Chai, W., Du, Q., Shay, J. W., & Wright, W. E. (2006). Human telomeres have different overhang sizes at leading versus lagging strands. Molecular cell, 21(3), 427-435. PMID: 16455497 DOI: 10.1016/j.molcel.2005.12.004</ref> Endogenous G4 (eG4), with its unique secondary structure, is involved in a variety of important biological processes such as gene transcription, translation regulation, telomere extension, and chromatin modification. <ref name="In vivo" >Zhang, Z. H., Qian, S. H., Wei, D., & Chen, Z. X. (2023). In vivo dynamics and regulation of DNA G-quadruplex structures in mammals. Cell & Bioscience, 13(1), 117. PMID: 37381029 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303365 PMC10303365] DOI: 10.1186/s13578-023-01074-8</ref>

			The structures of eG4s are affected by interacting proteins in vivo. During DNA replication, dsDNA is unwound into ssDNA by helicases and stabilized by ssDNA-binding proteins. During transcription, the promoter TATA box interacts with TFIIH to melt the promoter. As a kind of nucleic acid structures, eG4s will inevitably be regulated by interacting proteins. The proteins that can interact with eG4s can be divided into two types according to their functions: one is the protein that can unfold eG4s (such as G4 helicase), and the other is the protein that can bind and stabilize eG4s. These two types of proteins together regulate the dynamics of eG4s in vivo.<ref name="In vivo" />

	Transcription of the C-rich telomeric strand generates a class of telomeric repeat-containing RNAs called TERRA (TElomere Repeat-containing RNA) with distinct subtelomeric sequences at their 5′ end and '''the same G-rich telomeric sequence at their 3′ end'''. These features are shared by TERRA molecules expressed by all the organisms studied to date.<ref>Barral, A., & Déjardin, J. (2020). Telomeric chromatin and TERRA. Journal of molecular biology, 432(15), 4244-4256. PMID: 32151584 DOI: 10.1016/j.jmb.2020.03.003</ref> Recent evidence indicates that aging is a condition which results in upregulation of TERRA in different cellular settings.<ref>Rivosecchi, J., & Cusanelli, E. (2023). TERRA beyond cancer: the biology of telomeric repeat‐containing RNAs in somatic and germ cells. Frontiers in Aging, 4. PMID: 37636218 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448526/ PMC10448526] DOI: 10.3389/fragi.2023.1224225</ref><ref>Canale, P., Campolo, J., Borghini, A., & Andreassi, M. G. (2023). Long Telomeric Repeat-Containing RNA (TERRA): Biological Functions and Challenges in Vascular Aging and Disease. Biomedicines, 11(12), 3211. PMID: 38137431 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740775/ PMC10740775] DOI: 10.3390/biomedicines11123211</ref> The G-quadruplex structure of TERRA is an important recognition element for the TRF2 shelterin subunit and physically interacts with it to bind to telomeric DNA and also with TRF1 to preserve the telomere’s structural stability.<ref>Abreu, P. L., Lee, Y. W., & Azzalin, C. M. (2022). In Vitro Characterization of the Physical Interactions between the Long Noncoding RNA TERRA and the Telomeric Proteins TRF1 and TRF2. International Journal of Molecular Sciences, 23(18), 10463. PMID: 36142374 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500956 PMC9500956] DOI: 10.3390/ijms231810463</ref><ref>Rivosecchi, J., Jurikova, K., & Cusanelli, E. (2024). Telomere-specific regulation of TERRA and its impact on telomere stability. In Seminars in Cell & Developmental Biology (Vol. 157, pp. 3-23). Academic Press.</ref>		Transcription of the C-rich telomeric strand generates a class of telomeric repeat-containing RNAs called TERRA (TElomere Repeat-containing RNA) with distinct subtelomeric sequences at their 5′ end and '''the same G-rich telomeric sequence at their 3′ end'''. These features are shared by TERRA molecules expressed by all the organisms studied to date.<ref>Barral, A., & Déjardin, J. (2020). Telomeric chromatin and TERRA. Journal of molecular biology, 432(15), 4244-4256. PMID: 32151584 DOI: 10.1016/j.jmb.2020.03.003</ref> Recent evidence indicates that aging is a condition which results in upregulation of TERRA in different cellular settings.<ref>Rivosecchi, J., & Cusanelli, E. (2023). TERRA beyond cancer: the biology of telomeric repeat‐containing RNAs in somatic and germ cells. Frontiers in Aging, 4. PMID: 37636218 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448526/ PMC10448526] DOI: 10.3389/fragi.2023.1224225</ref><ref>Canale, P., Campolo, J., Borghini, A., & Andreassi, M. G. (2023). Long Telomeric Repeat-Containing RNA (TERRA): Biological Functions and Challenges in Vascular Aging and Disease. Biomedicines, 11(12), 3211. PMID: 38137431 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740775/ PMC10740775] DOI: 10.3390/biomedicines11123211</ref> The G-quadruplex structure of TERRA is an important recognition element for the TRF2 shelterin subunit and physically interacts with it to bind to telomeric DNA and also with TRF1 to preserve the telomere’s structural stability.<ref>Abreu, P. L., Lee, Y. W., & Azzalin, C. M. (2022). In Vitro Characterization of the Physical Interactions between the Long Noncoding RNA TERRA and the Telomeric Proteins TRF1 and TRF2. International Journal of Molecular Sciences, 23(18), 10463. PMID: 36142374 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500956 PMC9500956] DOI: 10.3390/ijms231810463</ref><ref>Rivosecchi, J., Jurikova, K., & Cusanelli, E. (2024). Telomere-specific regulation of TERRA and its impact on telomere stability. In Seminars in Cell & Developmental Biology (Vol. 157, pp. 3-23). Academic Press.</ref>

Dmitry Dzhagarov at 13:02, 11 January 2024

2024-01-11T13:02:52Z

← Older revision		Revision as of 13:02, 11 January 2024
Line 4:		Line 4:

	The formation of telomeric quadruplexes has been shown to decrease the activity of the enzyme telomerase, which is responsible for elongating telomeres.<ref>Fletcher, T. M., Sun, D., Salazar, M., & Hurley, L. H. (1998). Effect of DNA secondary structure on human telomerase activity. Biochemistry, 37(16), 5536-5541. PMID: 9548937 DOI: 10.1021/bi972681p</ref><ref>Bryan, T. M. (2020). G-quadruplexes at telomeres: friend or foe?. Molecules, 25(16), 3686. PMID: 32823549 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464828/ PMC7464828] DOI: 10.3390/molecules25163686</ref>		The formation of telomeric quadruplexes has been shown to decrease the activity of the enzyme telomerase, which is responsible for elongating telomeres.<ref>Fletcher, T. M., Sun, D., Salazar, M., & Hurley, L. H. (1998). Effect of DNA secondary structure on human telomerase activity. Biochemistry, 37(16), 5536-5541. PMID: 9548937 DOI: 10.1021/bi972681p</ref><ref>Bryan, T. M. (2020). G-quadruplexes at telomeres: friend or foe?. Molecules, 25(16), 3686. PMID: 32823549 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464828/ PMC7464828] DOI: 10.3390/molecules25163686</ref>




			High occurrences of oxidized guanines in G4 structures due to the oxidative stress occurring under the influence of the reactive oxygen species (ROS) affects the genome stability and promotes mutagenesis, that can destabilize the stacking of guanin, senescence, and other age-related diseases.<ref>Bielskutė, S., Plavec, J., & Podbevšek, P. (2019). Impact of oxidative lesions on the human telomeric G-quadruplex. Journal of the American Chemical Society, 141(6), 2594-2603. PMID: 30657306 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727377 PMC6727377] DOI: 10.1021/jacs.8b12748</ref><ref>Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., ... & Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical interventions in aging, 757-772. PMID: 29731617 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927356 PMC5927356] DOI: 10.2147/CIA.S158513</ref> G4s in CDS (the coding sequence, that codes for a protein) and CpG regions (that contain several CpG methylated sequences of DNA) are the least likely regions to be affected by mutations, while enhancers and intergenic G4s are prone to higher variant-induced stabilization and destabilization due to the single-nucleotide variants.<ref>Neupane, A., Chariker, J. H., & Rouchka, E. C. (2023). Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states. Genes, 14(12), 2125. PMID: 36778288 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915501 PMC9915501] DOI: 10.1101/2023.01.30.526341</ref>

Dmitry Dzhagarov at 11:22, 11 January 2024

2024-01-11T11:22:55Z

← Older revision		Revision as of 11:22, 11 January 2024
Line 1:		Line 1:
			Nucleic acid sequences rich in guanine are capable of forming '''four-stranded structures called G-quadruplexes(G4)''', stabilized by hydrogen bonding between a tetrad of guanine bases<ref>Sen D, Gilbert W (1988). Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228</ref> and it generally extends over the C-rich strand forming a 3′ overhang reaching approximately 50–300 nucleotides in mammals.<ref>Chai, W., Du, Q., Shay, J. W., & Wright, W. E. (2006). Human telomeres have different overhang sizes at leading versus lagging strands. Molecular cell, 21(3), 427-435. PMID: 16455497 DOI: 10.1016/j.molcel.2005.12.004</ref>

			Transcription of the C-rich telomeric strand generates a class of telomeric repeat-containing RNAs called TERRA (TElomere Repeat-containing RNA) with distinct subtelomeric sequences at their 5′ end and '''the same G-rich telomeric sequence at their 3′ end'''. These features are shared by TERRA molecules expressed by all the organisms studied to date.<ref>Barral, A., & Déjardin, J. (2020). Telomeric chromatin and TERRA. Journal of molecular biology, 432(15), 4244-4256. PMID: 32151584 DOI: 10.1016/j.jmb.2020.03.003</ref> Recent evidence indicates that aging is a condition which results in upregulation of TERRA in different cellular settings.<ref>Rivosecchi, J., & Cusanelli, E. (2023). TERRA beyond cancer: the biology of telomeric repeat‐containing RNAs in somatic and germ cells. Frontiers in Aging, 4. PMID: 37636218 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448526/ PMC10448526] DOI: 10.3389/fragi.2023.1224225</ref><ref>Canale, P., Campolo, J., Borghini, A., & Andreassi, M. G. (2023). Long Telomeric Repeat-Containing RNA (TERRA): Biological Functions and Challenges in Vascular Aging and Disease. Biomedicines, 11(12), 3211. PMID: 38137431 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740775/ PMC10740775] DOI: 10.3390/biomedicines11123211</ref> The G-quadruplex structure of TERRA is an important recognition element for the TRF2 shelterin subunit and physically interacts with it to bind to telomeric DNA and also with TRF1 to preserve the telomere’s structural stability.<ref>Abreu, P. L., Lee, Y. W., & Azzalin, C. M. (2022). In Vitro Characterization of the Physical Interactions between the Long Noncoding RNA TERRA and the Telomeric Proteins TRF1 and TRF2. International Journal of Molecular Sciences, 23(18), 10463. PMID: 36142374 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500956 PMC9500956] DOI: 10.3390/ijms231810463</ref><ref>Rivosecchi, J., Jurikova, K., & Cusanelli, E. (2024). Telomere-specific regulation of TERRA and its impact on telomere stability. In Seminars in Cell & Developmental Biology (Vol. 157, pp. 3-23). Academic Press.</ref>

			The formation of telomeric quadruplexes has been shown to decrease the activity of the enzyme telomerase, which is responsible for elongating telomeres.<ref>Fletcher, T. M., Sun, D., Salazar, M., & Hurley, L. H. (1998). Effect of DNA secondary structure on human telomerase activity. Biochemistry, 37(16), 5536-5541. PMID: 9548937 DOI: 10.1021/bi972681p</ref><ref>Bryan, T. M. (2020). G-quadruplexes at telomeres: friend or foe?. Molecules, 25(16), 3686. PMID: 32823549 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464828/ PMC7464828] DOI: 10.3390/molecules25163686</ref>




	<ref>Sen D, Gilbert W (1988). Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228</ref>
	<ref>Routh ED, Creacy SD, Beerbower PE, Akman SA, Vaughn JP, Smaldino PJ (2017). A G-quadruplex DNA-affinity Approach for Purification of Enzymaticacvly Active G4 Resolvase1. Journal of Visualized Experiments. 121 (121). doi:10.3791/55496. PMC 5409278. PMID 28362374</ref>		<ref>Routh ED, Creacy SD, Beerbower PE, Akman SA, Vaughn JP, Smaldino PJ (2017). A G-quadruplex DNA-affinity Approach for Purification of Enzymaticacvly Active G4 Resolvase1. Journal of Visualized Experiments. 121 (121). doi:10.3791/55496. PMC 5409278. PMID 28362374</ref>
	<ref>Varshney, D., Spiegel, J., Zyner, K., Tannahill, D. & Balasubramanian, S. (2020). The regulation and functions of DNA and RNA G-quadruplexes. Nat Rev Mol Cell Biol 21, 459-474</ref>		<ref>Varshney, D., Spiegel, J., Zyner, K., Tannahill, D. & Balasubramanian, S. (2020). The regulation and functions of DNA and RNA G-quadruplexes. Nat Rev Mol Cell Biol 21, 459-474</ref>

Dmitry Dzhagarov: Created page with " Sen D, Gilbert W (1988). Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228 Routh ED, Creacy SD, Beerbower PE, Akman SA, Vaughn JP, Smaldino PJ (2017). A G-quadruplex DNA-affinity Approach for Purification of Enzymaticacvly Active G4 Resolvase1. Journal of Visualized Experiments. 121 (121). doi:10.3791/5..."

2024-01-11T08:00:53Z

Created page with " <ref>Sen D, Gilbert W (1988). Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228</ref> <ref>Routh ED, Creacy SD, Beerbower PE, Akman SA, Vaughn JP, Smaldino PJ (2017). A G-quadruplex DNA-affinity Approach for Purification of Enzymaticacvly Active G4 Resolvase1. Journal of Visualized Experiments. 121 (121). doi:10.3791/5..."

New page

<ref>Sen D, Gilbert W (1988). Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228</ref>
<ref>Routh ED, Creacy SD, Beerbower PE, Akman SA, Vaughn JP, Smaldino PJ (2017). A G-quadruplex DNA-affinity Approach for Purification of Enzymaticacvly Active G4 Resolvase1. Journal of Visualized Experiments. 121 (121). doi:10.3791/55496. PMC 5409278. PMID 28362374</ref>
<ref>Varshney, D., Spiegel, J., Zyner, K., Tannahill, D. & Balasubramanian, S. (2020). The regulation and functions of DNA and RNA G-quadruplexes. Nat Rev Mol Cell Biol 21, 459-474</ref>
<ref>Huppert, J. L., & Balasubramanian, S. (2005). Prevalence of quadruplexes in the human genome. Nucleic acids research, 33(9), 2908-2916. PMID: 15914667 PMCID: PMC1140081 DOI: 10.1093/nar/gki609</ref>
<ref>Biffi, G., Tannahill, D., McCafferty, J. & Balasubramanian, S. (2013). Quantitative visualization of DNA G-quadruplex structures in human cells. Nat Chem 5, 182-186</ref>
<ref>Hansel-Hertsch, R. et al. (2016). G-quadruplex structures mark human regulatory chromatin. Nature genetics 48, 1267-1272</ref>
<ref>Hansel-Hertsch, R., Spiegel, J., Marsico, G., Tannahill, D. & Balasubramanian, S. (2018). Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin immunoprecipitation and high-throughput sequencing. Nat Protoc 13, 551-564</ref>
<ref>Lyu, J., Shao, R., Kwong Yung, P. Y. & Elsasser, S. J. (2022). Genome-wide mapping of G766 quadruplex structures with CUT&Tag. Nucleic acids research 50, e13 (2022).</ref>
<ref>Muller, S., Kumari, S., Rodriguez, R. & Balasubramanian, S. (2010). Small-molecule-mediated G768 quadruplex isolation from human cells. Nat Chem 2, 1095-1098</ref>
<ref>Zhang, X., Spiegel, J., Martinez Cuesta, S., Adhikari, S. & Balasubramanian, S. (2021). Chemical profiling of DNA G-quadruplex-interacting proteins in live cells. Nat Chem 13, 626-633</ref>

<ref>Jin, W., Zheng, J., Xiao, Y., Ju, L., Chen, F., Fu, J., ... & Zhang, Y. (2024). A universal molecular mechanism driving aging. bioRxiv, 2024-01. https://doi.org/10.1101/2024.01.06.574476</ref>

[[Category:Drafts]]