Chromosome breakage after G2 checkpoint release |
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Authors: | Deckbar Dorothee Birraux Julie Krempler Andrea Tchouandong Leopoldine Beucher Andrea Walker Sarah Stiff Tom Jeggo Penny Löbrich Markus |
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Affiliation: | 1.Fachrichtung Biophysik, Universität des Saarlandes, 66421 Homburg/Saar, Germany; 2.Genome Damage and Stability Centre, University of Sussex, East Sussex BN1 9RQ, England, UK |
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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. |
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