ERCC1/XPF removes the 3' overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes - PubMed (original) (raw)
ERCC1/XPF removes the 3' overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes
Xu-Dong Zhu et al. Mol Cell. 2003 Dec.
Free article
Abstract
Human telomeres are protected by TRF2. Inhibition of this telomeric protein results in partial loss of the telomeric 3' overhang and chromosome end fusions formed through nonhomologous end-joining (NHEJ). Here we report that ERCC1/XPF-deficient cells retained the telomeric overhang after TRF2 inhibition, identifying this nucleotide excision repair endonuclease as the culprit in overhang removal. Furthermore, these cells did not accumulate telomere fusions, suggesting that overhang processing is a prerequisite for NHEJ of telomeres. ERCC1/XPF was also identified as a component of the telomeric TRF2 complex. ERCC1/XPF-deficient mouse cells had a novel telomere phenotype, characterized by Telomeric DNA-containing Double Minute chromosomes (TDMs). We speculate that TDMs are formed through the recombination of telomeres with interstitial telomere-related sequences and that ERCC1/XPF functions to repress this process. Collectively, these data reveal an unanticipated involvement of the ERCC1/XPF NER endonuclease in the regulation of telomere integrity and establish that TRF2 prevents NHEJ at telomeres through protection of the telomeric overhang from ERCC1/XPF.
Similar articles
- Human XPF controls TRF2 and telomere length maintenance through distinctive mechanisms.
Wu Y, Mitchell TR, Zhu XD. Wu Y, et al. Mech Ageing Dev. 2008 Oct;129(10):602-10. doi: 10.1016/j.mad.2008.08.004. Epub 2008 Sep 4. Mech Ageing Dev. 2008. PMID: 18812185 - XPF with mutations in its conserved nuclease domain is defective in DNA repair but functions in TRF2-mediated telomere shortening.
Wu Y, Zacal NJ, Rainbow AJ, Zhu XD. Wu Y, et al. DNA Repair (Amst). 2007 Feb 4;6(2):157-66. doi: 10.1016/j.dnarep.2006.09.005. Epub 2006 Oct 18. DNA Repair (Amst). 2007. PMID: 17055345 - Multiple roles for MRE11 at uncapped telomeres.
Deng Y, Guo X, Ferguson DO, Chang S. Deng Y, et al. Nature. 2009 Aug 13;460(7257):914-8. doi: 10.1038/nature08196. Epub 2009 Jul 26. Nature. 2009. PMID: 19633651 Free PMC article. - Role of the telomeric DNA-binding protein TRF2 in the stability of human chromosome ends.
Ancelin K, Brun C, Gilson E. Ancelin K, et al. Bioessays. 1998 Nov;20(11):879-83. doi: 10.1002/(SICI)1521-1878(199811)20:11<879::AID-BIES2>3.0.CO;2-I. Bioessays. 1998. PMID: 9872053 Review. - The ERCC1 and ERCC4 (XPF) genes and gene products.
Manandhar M, Boulware KS, Wood RD. Manandhar M, et al. Gene. 2015 Sep 15;569(2):153-61. doi: 10.1016/j.gene.2015.06.026. Epub 2015 Jun 12. Gene. 2015. PMID: 26074087 Free PMC article. Review.
Cited by
- Microglia-derived extracellular vesicles trigger age-related neurodegeneration upon DNA damage.
Arvanitaki ES, Goulielmaki E, Gkirtzimanaki K, Niotis G, Tsakani E, Nenedaki E, Rouska I, Kefalogianni M, Xydias D, Kalafatakis I, Psilodimitrakopoulos S, Karagogeos D, Schumacher B, Stratakis E, Garinis GA. Arvanitaki ES, et al. Proc Natl Acad Sci U S A. 2024 Apr 23;121(17):e2317402121. doi: 10.1073/pnas.2317402121. Epub 2024 Apr 18. Proc Natl Acad Sci U S A. 2024. PMID: 38635632 Free PMC article. - ERCC4: a potential regulatory factor in inflammatory bowel disease and inflammation-associated colorectal cancer.
Shi R, Wang S, Jiang Y, Zhong G, Li M, Sun Y. Shi R, et al. Front Endocrinol (Lausanne). 2024 Mar 7;15:1348216. doi: 10.3389/fendo.2024.1348216. eCollection 2024. Front Endocrinol (Lausanne). 2024. PMID: 38516408 Free PMC article. Review. - The crosstalk between telomeres and DNA repair mechanisms: an overview to mammalian somatic cells, germ cells, and preimplantation embryos.
Tire B, Talibova G, Ozturk S. Tire B, et al. J Assist Reprod Genet. 2024 Feb;41(2):277-291. doi: 10.1007/s10815-023-03008-2. Epub 2024 Jan 2. J Assist Reprod Genet. 2024. PMID: 38165506 Review. - Telomeres as hotspots for innate immunity and inflammation.
Nassour J, Przetocka S, Karlseder J. Nassour J, et al. DNA Repair (Amst). 2024 Jan;133:103591. doi: 10.1016/j.dnarep.2023.103591. Epub 2023 Nov 5. DNA Repair (Amst). 2024. PMID: 37951043 Free PMC article. Review. - XPF interacts with TOP2B for R-loop processing and DNA looping on actively transcribed genes.
Chatzinikolaou G, Stratigi K, Siametis A, Goulielmaki E, Akalestou-Clocher A, Tsamardinos I, Topalis P, Austin C, Bouwman BAM, Crosetto N, Altmüller J, Garinis GA. Chatzinikolaou G, et al. Sci Adv. 2023 Nov 10;9(45):eadi2095. doi: 10.1126/sciadv.adi2095. Epub 2023 Nov 8. Sci Adv. 2023. PMID: 37939182 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous