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Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8173-8. Epub 2002 May 28.

Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX.

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  • 1Howard Hughes Medical Institute, Department of Genetics, Children's Hospital, Boston, MA 02115, USA.

Abstract

In mammalian cells, DNA double-strand breaks (DSBs) cause rapid phosphorylation of the H2AX core histone variant (to form gamma-H2AX) in megabase chromatin domains flanking sites of DNA damage. To investigate the role of H2AX in mammalian cells, we generated H2AX-deficient (H2AX(Delta)/Delta) mouse embryonic stem (ES) cells. H2AX(Delta)/Delta ES cells are viable. However, they are highly sensitive to ionizing radiation (IR) and exhibit elevated levels of spontaneous and IR-induced genomic instability. Notably, H2AX is not required for NHEJ per se because H2AX(Delta)/Delta ES cells support normal levels and fidelity of V(D)J recombination in transient assays and also support lymphocyte development in vivo. However, H2AX(Delta)/Delta ES cells exhibit altered IR-induced BRCA1 focus formation. Our findings indicate that H2AX function is essential for mammalian DNA repair and genomic stability.

PMID:
12034884
[PubMed - indexed for MEDLINE]
PMCID:
PMC123040
Free PMC Article
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