And Yet, It Moves: Nuclear and Chromatin Dynamics of a Heterochromatic Double-strand Break

Overview

Journal Philos Trans R Soc Lond B Biol Sci

Specialty Biology

Date 2017 Aug 30

PMID 28847828

Citations 31

Authors

P Christopher Caridi

Laetitia Delabaere

Grzegorz Zapotoczny

Irene Chiolo

Affiliations

Soon will be listed here.

Abstract

Heterochromatin is mostly composed of repeated DNA sequences prone to aberrant recombination. How cells maintain the stability of these sequences during double-strand break (DSB) repair has been a long-standing mystery. Studies in cells revealed that faithful homologous recombination repair of heterochromatic DSBs relies on the striking relocalization of repair sites to the nuclear periphery before Rad51 recruitment and repair progression. Here, we summarize our current understanding of this response, including the molecular mechanisms involved, and conserved pathways in mammalian cells. We will highlight important similarities with pathways identified in budding yeast for repair of other types of repeated sequences, including rDNA and short telomeres. We will also discuss the emerging role of chromatin composition and regulation in heterochromatin repair progression. Together, these discoveries challenged previous assumptions that repair sites are substantially static in multicellular eukaryotes, that heterochromatin is largely inert in the presence of DSBs, and that silencing and compaction in this domain are obstacles to repair.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.

Citing Articles

Replication fork stalling in late S-phase elicits nascent strand degradation by DNA mismatch repair.

Colicino-Murbach E, Hathaway C, Dungrawala H Nucleic Acids Res. 2024; 52(18):10999-11013.

PMID: 39180395 PMC: 11472054. DOI: 10.1093/nar/gkae721.

"Off-pore" nucleoporins relocalize heterochromatic breaks through phase separation.

Merigliano C, Ryu T, See C, Caridi C, Li X, Butova N bioRxiv. 2024; .

PMID: 39071440 PMC: 11275802. DOI: 10.1101/2023.12.07.570729.

Nup153 is not required for anchoring heterochromatic DSBs to the nuclear periphery.

Ryu T, Merigliano C, Chiolo I MicroPubl Biol. 2024; 2024.

PMID: 38737725 PMC: 11087819. DOI: 10.17912/micropub.biology.001176.

Emergence and influence of sequence bias in evolutionarily malleable, mammalian tandem arrays.

Brovkina M, Chapman M, Holding M, Clowney E BMC Biol. 2023; 21(1):179.

PMID: 37612705 PMC: 10463633. DOI: 10.1186/s12915-023-01673-4.

Histone acetylation dynamics in repair of DNA double-strand breaks.

Aricthota S, Rana P, Haldar D Front Genet. 2022; 13:926577.

PMID: 36159966 PMC: 9503837. DOI: 10.3389/fgene.2022.926577.

References

Marnef A, Legube G . Organizing DNA repair in the nucleus: DSBs hit the road. Curr Opin Cell Biol. 2017; 46:1-8. DOI: 10.1016/j.ceb.2016.12.003. View

Hauer M, Seeber A, Singh V, Thierry R, Sack R, Amitai A . Histone degradation in response to DNA damage enhances chromatin dynamics and recombination rates. Nat Struct Mol Biol. 2017; 24(2):99-107. DOI: 10.1038/nsmb.3347. View

Swartz R, Rodriguez E, King M . A role for nuclear envelope-bridging complexes in homology-directed repair. Mol Biol Cell. 2014; 25(16):2461-71. PMC: 4142617. DOI: 10.1091/mbc.E13-10-0569. View

Zarebski M, Wiernasz E, Dobrucki J . Recruitment of heterochromatin protein 1 to DNA repair sites. Cytometry A. 2009; 75(7):619-25. DOI: 10.1002/cyto.a.20734. View

Shumaker D, Dechat T, Kohlmaier A, Adam S, Bozovsky M, Erdos M . Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci U S A. 2006; 103(23):8703-8. PMC: 1472659. DOI: 10.1073/pnas.0602569103. View

Groocock L, Nie M, Prudden J, Moiani D, Wang T, Cheltsov A . RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response. EMBO Rep. 2014; 15(5):601-8. PMC: 4210088. DOI: 10.1002/embr.201338369. View

Freudenreich C, Su X . Relocalization of DNA lesions to the nuclear pore complex. FEMS Yeast Res. 2016; 16(8). PMC: 5113167. DOI: 10.1093/femsyr/fow095. View

Goodarzi A, Kurka T, Jeggo P . KAP-1 phosphorylation regulates CHD3 nucleosome remodeling during the DNA double-strand break response. Nat Struct Mol Biol. 2011; 18(7):831-9. DOI: 10.1038/nsmb.2077. View

Krawczyk P, Borovski T, Stap J, Cijsouw T, Ten Cate R, Medema J . Chromatin mobility is increased at sites of DNA double-strand breaks. J Cell Sci. 2012; 125(Pt 9):2127-33. DOI: 10.1242/jcs.089847. View

10.

Hoffman M, Ernst J, Wilder S, Kundaje A, Harris R, Libbrecht M . Integrative annotation of chromatin elements from ENCODE data. Nucleic Acids Res. 2012; 41(2):827-41. PMC: 3553955. DOI: 10.1093/nar/gks1284. View

11.

Tjong H, Li W, Kalhor R, Dai C, Hao S, Gong K . Population-based 3D genome structure analysis reveals driving forces in spatial genome organization. Proc Natl Acad Sci U S A. 2016; 113(12):E1663-72. PMC: 4812752. DOI: 10.1073/pnas.1512577113. View

12.

Sinha S, Li F, Villarreal D, Shim J, Yoon S, Myung K . Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions. PLoS Genet. 2017; 13(4):e1006714. PMC: 5413072. DOI: 10.1371/journal.pgen.1006714. View

13.

Sukup-Jackson M, Kiraly O, Kay J, Na L, Rowland E, Winther K . Rosa26-GFP direct repeat (RaDR-GFP) mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo. PLoS Genet. 2014; 10(6):e1004299. PMC: 4046920. DOI: 10.1371/journal.pgen.1004299. View

14.

Dion V, Kalck V, Seeber A, Schleker T, Gasser S . Cohesin and the nucleolus constrain the mobility of spontaneous repair foci. EMBO Rep. 2013; 14(11):984-91. PMC: 3818071. DOI: 10.1038/embor.2013.142. View

15.

Chiolo I, Minoda A, Colmenares S, Polyzos A, Costes S, Karpen G . Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell. 2011; 144(5):732-44. PMC: 3417143. DOI: 10.1016/j.cell.2011.02.012. View

16.

Aten J, Stap J, Krawczyk P, van Oven C, Hoebe R, Essers J . Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains. Science. 2004; 303(5654):92-5. DOI: 10.1126/science.1088845. View

17.

Janssen A, Breuer G, Brinkman E, van der Meulen A, Borden S, van Steensel B . A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin. Genes Dev. 2016; 30(14):1645-57. PMC: 4973294. DOI: 10.1101/gad.283028.116. View

18.

Noon A, Shibata A, Rief N, Lobrich M, Stewart G, Jeggo P . 53BP1-dependent robust localized KAP-1 phosphorylation is essential for heterochromatic DNA double-strand break repair. Nat Cell Biol. 2010; 12(2):177-84. DOI: 10.1038/ncb2017. View

19.

Alagoz M, Katsuki Y, Ogiwara H, Ogi T, Shibata A, Kakarougkas A . SETDB1, HP1 and SUV39 promote repositioning of 53BP1 to extend resection during homologous recombination in G2 cells. Nucleic Acids Res. 2015; 43(16):7931-44. PMC: 4652757. DOI: 10.1093/nar/gkv722. View

20.

Hunt C, Ramnarain D, Horikoshi N, Iyengar P, Pandita R, Shay J . Histone modifications and DNA double-strand break repair after exposure to ionizing radiations. Radiat Res. 2013; 179(4):383-92. PMC: 4133051. DOI: 10.1667/RR3308.2. View