Complementary functions of ATM and H2AX in development and suppression of genomic instability
2008; National Academy of Sciences; Volume: 105; Issue: 27 Linguagem: Inglês
10.1073/pnas.0803520105
ISSN1091-6490
AutoresShan Zha, JoAnn Sekiguchi, James W. Brush, Craig H. Bassing, Frederick W. Alt,
Tópico(s)Microtubule and mitosis dynamics
ResumoUpon DNA damage, histone H2AX is phosphorylated by ataxia-telangiectasia mutated (ATM) and other phosphoinositide 3-kinase-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 embryonic lethality and dramatic cellular genomic instability. Mechanistically, 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.
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