title: Control of sister chromatid recombination by histone H2AX.
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.
authors.affiliation: Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02115, USA.
authors.forename: Anyong
authors.initials: A
authors.lastname: Xie
authors.forename: Nadine
authors.initials: N
authors.lastname: Puget
authors.forename: Inbo
authors.initials: I
authors.lastname: Shim
authors.forename: Shobu
authors.initials: S
authors.lastname: Odate
authors.forename: Ingeborga
authors.initials: I
authors.lastname: Jarzyna
authors.forename: Craig H
authors.initials: CH
authors.lastname: Bassing
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Ralph
authors.initials: R
authors.lastname: Scully
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D051379:Mice; D051135:Rad51 Recombinase; D011995:Recombination, Genetic / Q000502:physiology*; D012694:Serine / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D006657:Histones; D051135:Rad51 Recombinase; D012694:Serine; C495154:Rad51 protein, mouse; C475961:gamma-H2AX protein, mouse