title: ATM signaling and genomic stability in response to DNA damage.
abstract: DNA double strand breaks represent the most threatening lesion to the integrity of the genome in cells exposed to ionizing radiation and radiomimetic chemicals. Those breaks are recognized, signaled to cell cycle checkpoints and repaired by protein complexes. The product of the gene (ATM) mutated in the human genetic disorder ataxia-telangiectasia (A-T) plays a central role in the recognition and signaling of DNA damage. ATM is one of an ever growing number of proteins which when mutated compromise the stability of the genome and predispose to tumour development. Mechanisms for recognising double strand breaks in DNA, maintaining genome stability and minimizing risk of cancer are discussed.
authors.affiliation: Queensland Cancer Fund Research Unit, The Queensland Institute of Medical Research, PO Box Royal Brisbane Hospital, Herston, Brisbane 4029, Australia. martinl@qimr.edu.au
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
authors.forename: Geoff
authors.initials: G
authors.lastname: Birrell
authors.forename: Philip
authors.initials: P
authors.lastname: Chen
authors.forename: Sergei
authors.initials: S
authors.lastname: Kozlov
authors.forename: Shaun
authors.initials: S
authors.lastname: Scott
authors.forename: Nuri
authors.initials: N
authors.lastname: Gueven
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000209:etiology / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004268:DNA-Binding Proteins; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases