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

ABSTRACT: Upon 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.

SUBMITTER: Zha S

PROVIDER: S-EPMC2453730 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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

Zha Shan S Sekiguchi JoAnn J Brush James W JW Bassing Craig H CH Alt Frederick W FW

Proceedings of the National Academy of Sciences of the United States of America 20080701 27

Upon 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, ...[more]

PMID: 18599436

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