Double strand break repair functions of histone H2AX

Chromosomal double strand breaks provoke an extensive reaction in neighboring chromatin, characterized by phosphorylation of histone H2AX on serine 139 of its C-terminal tail (to form "gamma H2AX"). The gamma H2AX response contributes to the repair of double strand breaks encountered in a variety of different contexts, including those induced by ionizing radiation, physiologically programmed breaks that characterize normal immune cell development and the pathological exposure of DNA ends triggered by telomere dysfunction. gamma H2AX also participates in the evolutionarily conserved process of sister chromatid recombination, a homologous recombination pathway involved in the suppression of genomic instability during DNA replication and directly implicated in tumor suppression. At a biochemical level, the gamma H2AX response provides a compelling example of how the "histone code" is adapted to the regulation of double strand break repair. Here, we review progress in research aimed at understanding how gamma H2AX contributes to double strand break repair in mammalian cells. (C) 2013 Elsevier B.V. All rights reserved.