Akt/PKB suppresses DNA damage processing and checkpoint activation in late G2

Xu, Naihan, Hegarat, Nadia, Black, Elizabeth J, Scott, Mary T, Hochegger, Helfrid and Gillespie, David A. (2010) Akt/PKB suppresses DNA damage processing and checkpoint activation in late G2. Journal of Cell Biology, 190 (3). pp. 297-305. ISSN 0021-9525

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Using 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 γ-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

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Depositing User: Helfrid Hochegger
Date Deposited: 06 Feb 2012 20:53
Last Modified: 01 Feb 2013 12:23
URI: http://srodev.sussex.ac.uk/id/eprint/28618
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