New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin - PubMed (original) (raw)
Review
. 2002 Jan 21;21(4):553-63.
doi: 10.1038/sj.onc.1205082.
Affiliations
- PMID: 11850780
- DOI: 10.1038/sj.onc.1205082
Review
New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin
Simon W-L Chan et al. Oncogene. 2002.
Abstract
Telomeres are stabilized, and telomeric DNA is replenished, by the action of the ribonucleoprotein reverse transcriptase telomerase. Telomere capping functions include the ability of telomeres to protect chromosome ends from cellular DNA-damage responses such as cell cycle arrest or apoptosis. This property of telomeres is especially important for cancer cells, which continue proliferating despite chromosome aberrations. Telomere capping is influenced by multiple, mutually reinforcing factors including telomere length, although telomere length is only one of several determinants of telomere functionality. For example, many cancer cells express high levels of telomerase yet maintain relatively short telomeres. We consider three aspects of telomere capping that have emerged relatively recently: (1) a new role for telomerase in telomere capping independent of its function in telomere elongation. Support for this novel function comes from experiments showing an increase in replicative potential with the reactivation of telomerase, without net telomere lengthening; (2) the role at telomeres of DNA damage proteins. We propose a model in which two factors specifically target telomeres for the action of telomerase, as opposed to recombination or non-homologous end-joining: binding by telomeric proteins that limits DNA damage responses at telomeres, and the affinity of the telomerase RNP for telomeric proteins and DNA; and (3) we discuss a potential protective role of amplified subtelomeric DNAs, which may aid capping of telomeres maintained by non-telomerase based mechanisms through the formation of heterochromatin.
Similar articles
- Telomeres, telomerase and chromosome stability.
Preston RJ. Preston RJ. Radiat Res. 1997 May;147(5):529-34. Radiat Res. 1997. PMID: 9146697 Review. - Critically short telomeres in acute myeloid leukemia with loss or gain of parts of chromosomes.
Swiggers SJ, Kuijpers MA, de Cort MJ, Beverloo HB, Zijlmans JM. Swiggers SJ, et al. Genes Chromosomes Cancer. 2006 Mar;45(3):247-56. doi: 10.1002/gcc.20286. Genes Chromosomes Cancer. 2006. PMID: 16281260 - Telomeres, telomerase, and apoptosis.
Mondello C, Scovassi AI. Mondello C, et al. Biochem Cell Biol. 2004 Aug;82(4):498-507. doi: 10.1139/o04-048. Biochem Cell Biol. 2004. PMID: 15284903 Review. - Senescence and immortalization: role of telomeres and telomerase.
Shay JW, Wright WE. Shay JW, et al. Carcinogenesis. 2005 May;26(5):867-74. doi: 10.1093/carcin/bgh296. Epub 2004 Oct 7. Carcinogenesis. 2005. PMID: 15471900 Review. - The role of telomeres and telomerase complex in haematological neoplasia: the length of telomeres as a marker of carcinogenesis and prognosis of disease.
Gancarcíková M, Zemanová Z, Brezinová J, Berková A, Vcelíková S, Smigová J, Michalová K. Gancarcíková M, et al. Prague Med Rep. 2010;111(2):91-105. Prague Med Rep. 2010. PMID: 20653999 Review.
Cited by
- Telomere dynamics in human pluripotent stem cells.
Ma B, Martínez P, Sánchez-Vázquez R, Blasco MA. Ma B, et al. Cell Cycle. 2023 Dec-Dec;22(23-24):2505-2521. doi: 10.1080/15384101.2023.2285551. Epub 2024 Jan 14. Cell Cycle. 2023. PMID: 38219218 Free PMC article. - Recent advancements in the structural biology of human telomerase and their implications for improved design of cancer therapeutics.
Welfer GA, Freudenthal BD. Welfer GA, et al. NAR Cancer. 2023 Mar 3;5(1):zcad010. doi: 10.1093/narcan/zcad010. eCollection 2023 Mar. NAR Cancer. 2023. PMID: 36879683 Free PMC article. - Telomeres and Telomerase in the Control of Stem Cells.
Lupatov AY, Yarygin KN. Lupatov AY, et al. Biomedicines. 2022 Sep 20;10(10):2335. doi: 10.3390/biomedicines10102335. Biomedicines. 2022. PMID: 36289597 Free PMC article. Review. - Dual effects of supplemental oxygen on pulmonary infection, inflammatory lung injury, and neuromodulation in aging and COVID-19.
Lin M, Stewart MT, Zefi S, Mateti KV, Gauthier A, Sharma B, Martinez LR, Ashby CR Jr, Mantell LL. Lin M, et al. Free Radic Biol Med. 2022 Sep;190:247-263. doi: 10.1016/j.freeradbiomed.2022.08.004. Epub 2022 Aug 11. Free Radic Biol Med. 2022. PMID: 35964839 Free PMC article. Review. - DNA Damage Response-Associated Cell Cycle Re-Entry and Neuronal Senescence in Brain Aging and Alzheimer's Disease.
Wong GC, Chow KH. Wong GC, et al. J Alzheimers Dis. 2023;94(s1):S429-S451. doi: 10.3233/JAD-220203. J Alzheimers Dis. 2023. PMID: 35848025 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources