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Chromosome breakage after G2 checkpoint release

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posted on 2023-06-07, 14:44 authored by Dorothee Deckbar, Julie Birraux, Andrea Krempler, Leopoldine Tchouandong, Andrea Beucher, Sarah Walker, Thomas Stiff, Penny Jeggo, Markus Löbrich
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.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Journal of Cell Biology

ISSN

0021-9525

Publisher

Rockefeller University Press

Issue

6

Volume

176

Page range

749-755

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2008-09-30

First Open Access (FOA) Date

2018-05-08

First Compliant Deposit (FCD) Date

2019-07-02

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