Aarhus University Seal / Aarhus Universitets segl

The Caenorhabditis elegans Werner syndrome protein participates in DNA damage checkpoint and DNA repair in response to CPT-induced double-strand breaks

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Moonjung Hyun, Department of Life Sciences, University of Ulsan, Ulsan, Sydkorea
  • Seoyun Choi, Department of Life Sciences, University of Ulsan, Ulsan, Sydkorea
  • Tinna Stevnsner
  • Byungchan Ahn, Department of Life Sciences, University of Ulsan, Ulsan

The RecQ helicases play roles in maintenance of genomic stability in species ranging from Escherichia coli to humans and interact with proteins involved in DNA metabolic pathways such as DNA repair, recombination, and replication. Our previous studies found that the Caenorhabditis elegans WRN-1 RecQ protein (a human WRN ortholog) exhibits ATP-dependent 3'-5' helicase activity and that the WRN-1 helicase is stimulated by RPA-1 on a long forked DNA duplex. However, the role of WRN-1 in response to S-phase associated with DSBs is unclear. We found that WRN-1 is involved in the checkpoint response to DSBs after CPT, inducing cell cycle arrest, is recruited to DSBs by RPA-1 and functions upstream of ATL-1 and ATM-1 for CHK-1 phosphorylation in the S-phase checkpoint. In addition, WRN-1 and RPA-1 recruitments to the DSBs require MRE-11, suggesting that DSB processing controlled by MRE-11 is important for WRN-1 at DSBs. The repair of CPT-induced DSBs is greatly reduced in the absence of WRN-1. These observations suggest that WRN-1 functions downstream of RPA-1 and upstream of CHK-1 in the DSB checkpoint pathway and is also required for the repair of DSB.

OriginalsprogEngelsk
TidsskriftCellular Signalling
Vol/bind28
Nummer3
Sider (fra-til)214-223
Antal sider10
ISSN0898-6568
DOI
StatusUdgivet - 2016

Se relationer på Aarhus Universitet Citationsformater

ID: 95561038