Complementary functions of ATM and H2AX in development and suppression of genomic instability
- 8 July 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (27), 9302-9306
- https://doi.org/10.1073/pnas.0803520105
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.This publication has 32 references indexed in Scilit:
- DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombinationThe Journal of Experimental Medicine, 2008
- Base-excision repair of oxidative DNA damageNature, 2007
- Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6Cell, 2006
- Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cellsNature, 2004
- H2AX Haploinsufficiency Modifies Genomic Stability and Tumor SusceptibilityCell, 2003
- Phosphorylation of Histone H2AX and Activation of Mre11, Rad50, and Nbs1 in Response to Replication-dependent DNA Double-strand Breaks Induced by Mammalian DNA Topoisomerase I Cleavage ComplexesOnline Journal of Public Health Informatics, 2003
- 11q Deletions in Hematological MalignanciesLeukemia & Lymphoma, 2001
- Requirement for Atm in Ionizing Radiation-Induced Cell Death in the Developing Central Nervous SystemScience, 1998
- The Igκ 3′ Enhancer Influences the Ratio of Igκ versus Igλ B LymphocytesImmunity, 1996
- Atm-Deficient Mice: A Paradigm of Ataxia TelangiectasiaCell, 1996