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Complementary functions of ATM and H2AX in development and suppression of genomic instability
 

Summary: Complementary functions of ATM and H2AX in
development and suppression of genomic instability
Shan Zha, JoAnn Sekiguchi*, James W. Brush, Craig H. Bassing
, and Frederick W. Alt
Howard Hughes Medical Institute, Children's Hospital, Immune Disease Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02115
Contributed by Frederick W. Alt, April 11, 2008 (sent for review March 22, 2008)
Upon DNA damage, histone H2AX is phosphorylated by ataxia-
telangiectasia mutated (ATM) and other phosphoinositide 3-ki-
nase-related protein kinases. To elucidate further the potential
overlapping and unique functions of ATM and H2AX, we asked
whether they have synergistic functions in the development and
maintenance of genomic stability by inactivating both genes in
mouse germ line. Combined ATM/H2AX deficiency caused embry-
onic lethality and dramatic cellular genomic instability. Mechanis-
tically, severe genomic instability in the double-deficient cells is
associated with a requirement for H2AX to repair oxidative DNA
damage resulting from ATM deficiency. We discuss these findings
in the context of synergies between ATM and other repair factors.
DNA repair embryonic lethality oxidative DNA damage
DNA double-strand breaks (DSBs) can result from normal

  

Source: Alt,, Frederick - Immune Disease Institute, Harvard University

 

Collections: Biology and Medicine