DNA polymerase κ‐dependent DNA synthesis at stalled replication forks is important for CHK1 activation. (25th June 2013)

• Record Type: Journal Article
• Authors: Bétous, Rémy; Pillaire, Marie‐Jeanne; Pierini, Laura; van der Laan, Siem; Recolin, Bénédicte; Ohl‐Séguy, Emma; Guo, Caixia; Niimi, Naoko; Grúz, Petr; Nohmi, Takehiko; Friedberg, Errol; Cazaux, Christophe; Maiorano, Domenico; Hoffmann, Jean‐Sébastien
• Is Part Of: EMBO journal. Volume 32:Number 15(2013)
• Page Start: 2172
• Page End: 2185
• Publication Date: 2013-06-25
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.1038/emboj.2013.148
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Formation of primed single‐stranded DNA at stalled replication forks triggers activation of the replication checkpoint signalling cascade resulting in the ATR‐mediated phosphorylation of the Chk1 protein kinase, thus preventing genomic instability. By using siRNA‐mediated depletion in human cells and immunodepletion and reconstitution experiments in <italic>Xenopus</italic> egg extracts, we report that the Y‐family translesion (TLS) DNA polymerase kappa (Pol κ) contributes to the replication checkpoint response and is required for recovery after replication stress. We found that Pol κ is implicated in the synthesis of short DNA intermediates at stalled forks, facilitating the recruitment of the 9‐1‐1 checkpoint clamp. Furthermore, we show that Pol κ interacts with the Rad9 subunit of the 9‐1‐1 complex. Finally, we show that this novel checkpoint function of Pol κ is required for the maintenance of genomic stability and cell proliferation in unstressed human cells.</p> </abstract>