Send to

Choose Destination
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

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


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.

Comment in

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center