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

نویسندگان

  • Craig H Bassing
  • Katrin F Chua
  • JoAnn Sekiguchi
  • Heikyung Suh
  • Scott R Whitlow
  • James C Fleming
  • Brianna C Monroe
  • David N Ciccone
  • Catherine Yan
  • Katerina Vlasakova
  • David M Livingston
  • David O Ferguson
  • Ralph Scully
  • Frederick W Alt
چکیده

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.

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 99 12  شماره 

صفحات  -

تاریخ انتشار 2002