Chromosome breakage after G2 checkpoint release

Deckbar, Dorothee, Birraux, Julie, Krempler, Andrea, Tchouandong, Leopoldine, Beucher, Andrea, Walker, Sarah, Stiff, Tom, Jeggo, Penny and Löbrich, Markus (2007) Chromosome breakage after G2 checkpoint release. Journal of Cell Biology, 176 (6). pp. 749-755. ISSN 0021-9525

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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.

Item Type: Article
Keywords: Cell Cycle Proteins, DNA-Binding Proteins, Tumor Suppressor Proteins
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Gee Wheatley
Date Deposited: 30 Sep 2008
Last Modified: 16 Sep 2019 11:11
Google Scholar:93 Citations

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