Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products
作者： Song Zhao , Yi-Chinn Weng , Shyng-Shiou F. Yuan , Yi-Tzu Lin , Hao-Chi Hsu
DOI: 10.1038/35013083
关键词:
摘要: Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are recessive genetic disorders with susceptibility to cancer similar cellular phenotypes1. The protein product of the gene responsible for A-T, designated ATM, is a member family kinases characterized by carboxy-terminal phosphatidylinositol 3-kinase-like domain2,3. NBS1 specifically mutated in patients forms complex DNA repair proteins Rad50 Mre114,5,6,7. Here we show that phosphorylation NBS1, induced ionizing radiation, requires catalytically active ATM. Complexes containing ATM exist vivo both untreated cells treated radiation. We have identified two residues Ser 278 Ser 343 phosphorylated vitro whose modification essential response damage. This includes S-phase checkpoint activation, formation NBS1/Mre11/Rad50 nuclear foci rescue hypersensitivity Together, these results demonstrate biochemical link between cell-cycle checkpoints activated damage diseases overlapping phenotypes.
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