title: Chromosome breakage after G2 checkpoint release.
abstract: DNA double-strand break (DSB) repair and checkpoint control represent distinct mechanisms to reduce chromosomal instability. Ataxia telangiectasia (A-T) cells have checkpoint arrest and DSB repair defects. We examine the efficiency and interplay of ATM's G2 checkpoint and repair functions. Artemis cells manifest a repair defect identical and epistatic to A-T but show proficient checkpoint responses. Only a few G2 cells enter mitosis within 4 h after irradiation with 1 Gy but manifest multiple chromosome breaks. Most checkpoint-proficient cells arrest at the G2/M checkpoint, with the length of arrest being dependent on the repair capacity. Strikingly, cells released from checkpoint arrest display one to two chromosome breaks. This represents a major contribution to chromosome breakage. The presence of chromosome breaks in cells released from checkpoint arrest suggests that release occurs before the completion of DSB repair. Strikingly, we show that checkpoint release occurs at a point when approximately three to four premature chromosome condensation breaks and approximately 20 gammaH2AX foci remain.
authors.affiliation: Fachrichtung Biophysik, Universität des Saarlandes, 66421 Homburg/Saar, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Deckbar
authors.forename: Julie
authors.initials: J
authors.lastname: Birraux
authors.forename: Andrea
authors.initials: A
authors.lastname: Krempler
authors.forename: Leopoldine
authors.initials: L
authors.lastname: Tchouandong
authors.forename: Andrea
authors.initials: A
authors.lastname: Beucher
authors.forename: Sarah
authors.initials: S
authors.lastname: Walker
authors.forename: Tom
authors.initials: T
authors.lastname: Stiff
authors.forename: Penny
authors.initials: P
authors.lastname: Jeggo
authors.forename: Markus
authors.initials: M
authors.lastname: Löbrich
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D019457:Chromosome Breakage; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004720:Endonucleases; D016195:G2 Phase / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C426344:DCLRE1C protein, human; D004720:Endonucleases