Complementary functions of ATM and H2AX in development and suppression of genomic instability.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 18599436.
- Also identified by DOI 10.1073/pnas.0803520105 and PMC identifier 2453730.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
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.
Medical subject headings
- Cell Cycle Proteins
- DNA-Binding Proteins
- Genomic Instability
- Histones
- Protein Serine-Threonine Kinases
- Tumor Suppressor Proteins