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PMID: 15610743 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Control of sister chromatid recombination by histone H2AX.

Molecular cell ·Vol. 16 ·No. 6 ·2004-12-22 ·Pages 1017-25

Xie A, Puget N, Shim I, Odate S, Jarzyna I, Bassing CH, Alt FW, Scully R

Abstract

Histone H2AX has a role in suppressing genomic instability and cancer. However, the mechanisms by which it performs these functions are poorly understood. After DNA breakage, H2AX is phosphorylated on serine 139 in chromatin near the break. We show here that H2AX serine 139 enforces efficient homologous recombinational repair of a chromosomal double-strand break (DSB) by using the sister chromatid as a template. BRCA1, Rad51, and CHK2 contribute to recombinational repair, in part independently of H2AX. H2AX(-/-) cells show increased use of single-strand annealing, an error-prone deletional mechanism of DSB repair. Therefore, the chromatin response around a chromosomal DSB, in which H2AX serine 139 phosphorylation plays a central role, "shapes" the repair process in favor of potentially error-free interchromatid homologous recombination at the expense of error-prone repair. H2AX phosphorylation may help set up a favorable disposition between sister chromatids.

MeSH Terms
Animals BRCA1 Protein/metabolism Chromatids/metabolism DNA-Binding Proteins/metabolism Histones/metabolism Mice Rad51 Recombinase Recombination, Genetic/physiology Serine/metabolism
Chemicals
BRCA1 Protein DNA-Binding Proteins H2AX protein, mouse Histones Serine Rad51 Recombinase Rad51 protein, mouse
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Xie Anyong
Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02115, USA.
Puget Nadine
Shim Inbo
Odate Shobu
Jarzyna Ingeborga
Bassing Craig H
Alt Frederick W
Scully Ralph
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
DOI
10.1016/j.molcel.2004.12.007
Published
2004-12-22
Pages
1017-25
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2991138
Subset
IM
Grants
NCI NIH HHS · P01 CA109901 · United States
NCI NIH HHS · R01 CA095175 · United States
NCI NIH HHS · P01 CA092625 · United States
NCI NIH HHS · CA92625 · United States
NCI NIH HHS · R01 CA095175-03 · United States
NCI NIH HHS · CA109901 · United States
NCI NIH HHS · CA95175 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2004.12.007 PMC Full Text View journal details
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