The Emerging Role of Nuclear Architecture in DNA Repair and Genome Maintenance

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2009 Mar 12

PMID 19277046

Citations 239

Authors

Tom Misteli

Evi Soutoglou

Affiliations

Soon will be listed here.

Abstract

DNA repair and maintenance of genome stability are crucial to cellular and organismal function, and defects in these processes have been implicated in cancer and ageing. Detailed molecular, biochemical and genetic analyses have outlined the molecular framework involved in cellular DNA-repair pathways, but recent cell-biological approaches have revealed important roles for the spatial and temporal organization of the DNA-repair machinery during the recognition of DNA lesions and the assembly of repair complexes. It has also become clear that local higher-order chromatin structure, chromatin dynamics and non-random global genome organization are key factors in genome maintenance. These cell-biological features of DNA repair illustrate an emerging role for nuclear architecture in multiple aspects of genome maintenance.

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References

Wyman C, Kanaar R . DNA double-strand break repair: all's well that ends well. Annu Rev Genet. 2006; 40:363-83. DOI: 10.1146/annurev.genet.40.110405.090451. View

Meaburn K, Misteli T, Soutoglou E . Spatial genome organization in the formation of chromosomal translocations. Semin Cancer Biol. 2006; 17(1):80-90. PMC: 1805052. DOI: 10.1016/j.semcancer.2006.10.008. View

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

Qin S, Parthun M . Recruitment of the type B histone acetyltransferase Hat1p to chromatin is linked to DNA double-strand breaks. Mol Cell Biol. 2006; 26(9):3649-58. PMC: 1447429. DOI: 10.1128/MCB.26.9.3649-3658.2006. View

Kanaar R, Wyman C, Rothstein R . Quality control of DNA break metabolism: in the 'end', it's a good thing. EMBO J. 2008; 27(4):581-8. PMC: 2262039. DOI: 10.1038/emboj.2008.11. View

Papamichos-Chronakis M, Krebs J, Peterson C . Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell cycle checkpoint adaptation in response to DNA damage. Genes Dev. 2006; 20(17):2437-49. PMC: 1560417. DOI: 10.1101/gad.1440206. View

Tamburini B, Tyler J . Localized histone acetylation and deacetylation triggered by the homologous recombination pathway of double-strand DNA repair. Mol Cell Biol. 2005; 25(12):4903-13. PMC: 1140608. DOI: 10.1128/MCB.25.12.4903-4913.2005. View

Kusch T, Florens L, MacDonald W, Swanson S, Glaser R, Yates 3rd J . Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science. 2004; 306(5704):2084-7. DOI: 10.1126/science.1103455. View

Masumoto H, Hawke D, Kobayashi R, Verreault A . A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response. Nature. 2005; 436(7048):294-8. DOI: 10.1038/nature03714. View

10.

Costanzo V, Paull T, Gottesman M, Gautier J . Mre11 assembles linear DNA fragments into DNA damage signaling complexes. PLoS Biol. 2004; 2(5):E110. PMC: 406388. DOI: 10.1371/journal.pbio.0020110. View

11.

Bao Y, Shen X . Chromatin remodeling in DNA double-strand break repair. Curr Opin Genet Dev. 2007; 17(2):126-31. DOI: 10.1016/j.gde.2007.02.010. View

12.

Tyler J, Adams C, Chen S, Kobayashi R, Kamakaka R, Kadonaga J . The RCAF complex mediates chromatin assembly during DNA replication and repair. Nature. 1999; 402(6761):555-60. DOI: 10.1038/990147. View

13.

Celeste A, Difilippantonio S, Difilippantonio M, Fernandez-Capetillo O, Pilch D, Sedelnikova O . H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell. 2003; 114(3):371-383. PMC: 4737479. DOI: 10.1016/s0092-8674(03)00567-1. View

14.

Fernandez-Capetillo O, Chen H, Celeste A, Ward I, Romanienko P, Morales J . DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol. 2002; 4(12):993-7. DOI: 10.1038/ncb884. View

15.

Downs J, Lowndes N, Jackson S . A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature. 2001; 408(6815):1001-4. DOI: 10.1038/35050000. View

16.

Bencokova Z, Kaufmann M, Pires I, Lecane P, Giaccia A, Hammond E . ATM activation and signaling under hypoxic conditions. Mol Cell Biol. 2008; 29(2):526-37. PMC: 2612523. DOI: 10.1128/MCB.01301-08. View

17.

Wang B, Matsuoka S, Ballif B, Zhang D, Smogorzewska A, Gygi S . Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science. 2007; 316(5828):1194-8. PMC: 3573690. DOI: 10.1126/science.1139476. View

18.

Goodarzi A, Noon A, Deckbar D, Ziv Y, Shiloh Y, Lobrich M . ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell. 2008; 31(2):167-77. DOI: 10.1016/j.molcel.2008.05.017. View

19.

Keogh M, Kim J, Downey M, Fillingham J, Chowdhury D, Harrison J . A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature. 2005; 439(7075):497-501. DOI: 10.1038/nature04384. View

20.

Mitelman F, Johansson B, Mertens F . Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Nat Genet. 2004; 36(4):331-4. DOI: 10.1038/ng1335. View