No Overt Nucleosome Eviction at Deprotected Telomeres

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2008 Jul 16

PMID 18625717

Citations 22

Authors

Peng Wu

Titia de Lange

Affiliations

Soon will be listed here.

Abstract

Dysfunctional telomeres elicit the canonical DNA damage response, which includes the activation of the ATM or ATR kinase signaling pathways and end processing by nonhomologous end joining (NHEJ) or homologous recombination (HR). The cellular response to DNA double-strand breaks has been proposed to involve chromatin remodeling and nucleosome eviction, but whether dysfunctional telomeres undergo chromatin reorganization is not known. Here, we report on the nucleosomal organization of telomeres that have become deprotected through the deletion of the shelterin components TRF2 or POT1. We found no evidence of changes in the nucleosomal organization of the telomeric chromatin or nucleosome eviction near the telomere terminus. An unaltered chromatin structure was observed at telomeres lacking TRF2, which activate the ATM kinase and are a substrate for NHEJ. Similarly, telomeres lacking POT1a and POT1b, which activate the ATR kinase, showed no overt nucleosome eviction. Finally, telomeres lacking TRF2 and Ku70, which are processed by HR, appeared to maintain their original nucleosomal organization. We conclude that ATM signaling, ATR signaling, NHEJ, and HR at deprotected telomeres can take place in the absence of overt nucleosome eviction.

Citing Articles

Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization.

Lim C, Cech T Nat Rev Mol Cell Biol. 2021; 22(4):283-298.

PMID: 33564154 PMC: 8221230. DOI: 10.1038/s41580-021-00328-y.

BRM-SWI/SNF chromatin remodeling complex enables functional telomeres by promoting co-expression of TRF2 and TRF1.

Wu S, Ge Y, Li X, Yang Y, Zhou H, Lin K PLoS Genet. 2020; 16(6):e1008799.

PMID: 32502208 PMC: 7299400. DOI: 10.1371/journal.pgen.1008799.

Chromatin fiber structural motifs as regulatory hubs of genome function?.

Moraru M, Schalch T Essays Biochem. 2019; 63(1):123-132.

PMID: 30967476 PMC: 6484786. DOI: 10.1042/EBC20180065.

Emerging roles of telomeric chromatin alterations in cancer.

Cacchione S, Biroccio A, Rizzo A J Exp Clin Cancer Res. 2019; 38(1):21.

PMID: 30654820 PMC: 6337846. DOI: 10.1186/s13046-019-1030-5.

Local enrichment of HP1alpha at telomeres alters their structure and regulation of telomere protection.

Chow T, Shi X, Wei J, Guan J, Stadler G, Huang B Nat Commun. 2018; 9(1):3583.

PMID: 30181605 PMC: 6123478. DOI: 10.1038/s41467-018-05840-y.

References

Morrison A, Highland J, Krogan N, Arbel-Eden A, Greenblatt J, Haber J . INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Cell. 2004; 119(6):767-75. DOI: 10.1016/j.cell.2004.11.037. View

Wright W, Tesmer V, Huffman K, Levene S, Shay J . Normal human chromosomes have long G-rich telomeric overhangs at one end. Genes Dev. 1997; 11(21):2801-9. PMC: 316649. DOI: 10.1101/gad.11.21.2801. View

Hockemeyer D, Daniels J, Takai H, de Lange T . Recent expansion of the telomeric complex in rodents: Two distinct POT1 proteins protect mouse telomeres. Cell. 2006; 126(1):63-77. DOI: 10.1016/j.cell.2006.04.044. View

Konishi A, de Lange T . Cell cycle control of telomere protection and NHEJ revealed by a ts mutation in the DNA-binding domain of TRF2. Genes Dev. 2008; 22(9):1221-30. PMC: 2335317. DOI: 10.1101/gad.1634008. View

Kacian D, Spiegelman S . Use of micrococcal nuclease to monitor hybridization reactions with DNA. Anal Biochem. 1974; 58(2):534-40. DOI: 10.1016/0003-2697(74)90221-8. View

Lejnine S, Makarov V, Langmore J . Conserved nucleoprotein structure at the ends of vertebrate and invertebrate chromosomes. Proc Natl Acad Sci U S A. 1995; 92(6):2393-7. PMC: 42490. DOI: 10.1073/pnas.92.6.2393. View

Shim E, Hong S, Oum J, Yanez Y, Zhang Y, Lee S . RSC mobilizes nucleosomes to improve accessibility of repair machinery to the damaged chromatin. Mol Cell Biol. 2006; 27(5):1602-13. PMC: 1820475. DOI: 10.1128/MCB.01956-06. View

Makarov V, Lejnine S, Bedoyan J, Langmore J . Nucleosomal organization of telomere-specific chromatin in rat. Cell. 1993; 73(4):775-87. DOI: 10.1016/0092-8674(93)90256-p. View

Griffith J, Comeau L, Rosenfield S, Stansel R, Bianchi A, Moss H . Mammalian telomeres end in a large duplex loop. Cell. 1999; 97(4):503-14. DOI: 10.1016/s0092-8674(00)80760-6. View

10.

van Attikum H, Fritsch O, Gasser S . Distinct roles for SWR1 and INO80 chromatin remodeling complexes at chromosomal double-strand breaks. EMBO J. 2007; 26(18):4113-25. PMC: 2230671. DOI: 10.1038/sj.emboj.7601835. View

11.

Chai B, Huang J, Cairns B, Laurent B . Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair. Genes Dev. 2005; 19(14):1656-61. PMC: 1176001. DOI: 10.1101/gad.1273105. View

12.

Zhao Y, Hoshiyama H, Shay J, Wright W . Quantitative telomeric overhang determination using a double-strand specific nuclease. Nucleic Acids Res. 2007; 36(3):e14. PMC: 2241892. DOI: 10.1093/nar/gkm1063. View

13.

Takai H, Smogorzewska A, de Lange T . DNA damage foci at dysfunctional telomeres. Curr Biol. 2003; 13(17):1549-56. DOI: 10.1016/s0960-9822(03)00542-6. View

14.

Garcia-Cao M, OSullivan R, Peters A, Jenuwein T, Blasco M . Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat Genet. 2004; 36(1):94-9. DOI: 10.1038/ng1278. View

15.

Galati A, Rossetti L, Pisano S, Chapman L, Rhodes D, Savino M . The human telomeric protein TRF1 specifically recognizes nucleosomal binding sites and alters nucleosome structure. J Mol Biol. 2006; 360(2):377-85. DOI: 10.1016/j.jmb.2006.04.071. View

16.

Makarov V, Hirose Y, Langmore J . Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell. 1997; 88(5):657-66. DOI: 10.1016/s0092-8674(00)81908-x. View

17.

Wright J, Gottschling D, Zakian V . Saccharomyces telomeres assume a non-nucleosomal chromatin structure. Genes Dev. 1992; 6(2):197-210. DOI: 10.1101/gad.6.2.197. View

18.

Chai W, Du Q, Shay J, Wright W . Human telomeres have different overhang sizes at leading versus lagging strands. Mol Cell. 2006; 21(3):427-35. DOI: 10.1016/j.molcel.2005.12.004. View

19.

Hanish J, Yanowitz J, de Lange T . Stringent sequence requirements for the formation of human telomeres. Proc Natl Acad Sci U S A. 1994; 91(19):8861-5. PMC: 44706. DOI: 10.1073/pnas.91.19.8861. View

20.

Berkovich E, Monnat Jr R, Kastan M . Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nat Cell Biol. 2007; 9(6):683-90. DOI: 10.1038/ncb1599. View