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Akt/PKB suppresses DNA damage processing and checkpoint activation in late G2
journal contribution
posted on 2023-06-08, 08:10 authored by Naihan Xu, Nadia Hegarat, Elizabeth J Black, Mary T Scott, Helfrid HocheggerHelfrid Hochegger, David A. GillespieUsing chemical genetics to reversibly inhibit Cdk1, we find that cells arrested in late G2 are unable to delay mitotic entry after irradiation. Late G2 cells detect DNA damage lesions and form ?-H2AX foci but fail to activate Chk1. This reflects a lack of DNA double-strand break processing because late G2 cells fail to recruit RPA (replication protein A), ATR (ataxia telangiectasia and Rad3 related), Rad51, or CtIP (C-terminal interacting protein) to sites of radiation-induced damage, events essential for both checkpoint activation and initiation of DNA repair by homologous recombination. Remarkably, inhibition of Akt/PKB (protein kinase B) restores DNA damage processing and Chk1 activation after irradiation in late G2. These data demonstrate a previously unrecognized role for Akt in cell cycle regulation of DNA repair and checkpoint activation. Because Akt/PKB is frequently activated in many tumor types, these findings have important implications for the evolution and therapy of such cancers
History
Publication status
- Published
Journal
Journal of Cell BiologyISSN
0021-9525Publisher
Rockefeller University PressExternal DOI
Issue
3Volume
190Page range
297-305Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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