title: Sensing of intermediates in V(D)J recombination by ATM.
abstract: Ataxia-telangiectasia mutated (ATM) is required for resistance to radiation-induced DNA breaks. Here we use chromatin immunoprecipitation to show that ATM also localizes to breaks associated with V(D)J recombination. ATM recruitment to the recombining locus correlates approximately with recruitment of the break-initiating factor RAG1 and precedes efficient break repair, consistent with localization of ATM to normal recombination intermediates. A product of ATM kinase activity, Ser 18-phosphorylated p53, was detected similarly at these breaks, arguing that ATM phosphorylates target proteins in situ. We suggest routine surveillance of intermediates in V(D)J recombination by ATM helps suppress potentially oncogenic translocations when repair fails.
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Perkins
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Nair
authors.forename: Dale O
authors.initials: DO
authors.lastname: Cowley
authors.forename: Terry
authors.initials: T
authors.lastname: Van Dyke
authors.forename: Yung
authors.initials: Y
authors.lastname: Chang
authors.forename: Dale A
authors.initials: DA
authors.lastname: Ramsden
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins; D004254:DNA Nucleotidyltransferases / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051379:Mice; D016513:Mice, SCID; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011995:Recombination, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D045567:VDJ Recombinases
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases