title: The Caenorhabditis elegans Werner syndrome protein participates in DNA damage checkpoint and DNA repair in response to CPT-induced double-strand breaks.
abstract: 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.
authors.affiliation: Department of Life Sciences, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Moonjung
authors.initials: M
authors.lastname: Hyun
authors.affiliation: Department of Life Sciences, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Seoyun
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: Tinna
authors.initials: T
authors.lastname: Stevnsner
authors.affiliation: Department of Life Sciences, University of Ulsan, Ulsan, Republic of Korea. Electronic address: bbccahn@mail.ulsan.ac.kr.
authors.forename: Byungchan
authors.initials: B
authors.lastname: Ahn
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002166:Camptothecin / Q000633:toxicity*; D000071877:Checkpoint Kinase 1; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D016296:Mutagenesis; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D051716:Replication Protein A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects
chemical_list: D029742:Caenorhabditis elegans Proteins; D051716:Replication Protein A; C423224:mre-11 protein, C elegans; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605876:chk-1 protein, C elegans; D004265:DNA Helicases; C488009:WRN-1 protein, C elegans; D002166:Camptothecin
keywords: C. elegans; DNA damage checkpoint; DNA damage response; Werner syndrome protein