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EMBO J. 2013 Jul 31;32(15):2172-85. doi: 10.1038/emboj.2013.148. Epub 2013 Jun 25.

DNA polymerase κ-dependent DNA synthesis at stalled replication forks is important for CHK1 activation.

Author information

1
Equipe Labellisée La Ligue Contre le Cancer 2013, INSERM UMR 1037, CNRS ERL 505294, CRCT (Cancer Research Center of Toulouse), Toulouse, France.

Abstract

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 Xenopus 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.

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PMID:
23799366
PMCID:
PMC3730229
DOI:
10.1038/emboj.2013.148
[Indexed for MEDLINE]
Free PMC Article

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