Jul 29, 2004

H2AX: the histone guardian of the genome

DNA Repair
O Fernández-CapetilloAndré Nussenzweig

Abstract

At close hand to one's genomic material are the histones that make up the nucleosome. Standing guard, one variant stays hidden doubling as one of the core histones. But, thanks to its prime positioning, a variation in the tail of H2AX enables rapid modification of the histone code in response to DNA damage. A role for H2AX phosphorylation has been demonstrated in DNA repair, cell cycle checkpoints, regulated gene recombination events, and tumor suppression. In this review, we summarize what we have learned about this marker of DNA breaks, and highlight some of the questions that remain to be elucidated about the physiological role of H2AX. We also suggest a model in which chromatin restructuring mediated by H2AX phosphorylation serves to concentrate DNA repair/signaling factors and/or tether DNA ends together, which could explain the pleotropic phenotypes observed in its absence.

  • References75
  • Citations514

Mentioned in this Paper

CHEK2 wt Allele
Embryo
PRKDC gene
Non-Homologous DNA End-Joining
Biochemical Pathway
H2AFX gene
Nucleosomes
Histone antigen
Y Chromosome
Tumor Suppressor Genes

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