RRC ID 53442
Author Hyun M, Choi S, Stevnsner T, Ahn B.
Title The Caenorhabditis elegans Werner syndrome protein participates in DNA damage checkpoint and DNA repair in response to CPT-induced double-strand breaks.
Journal Cell Signal
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.
Volume 28(3)
Pages 214-223
Published 2016-3-1
DOI 10.1016/j.cellsig.2015.12.006
PII S0898-6568(15)30012-7
PMID 26691982
MeSH Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Camptothecin / toxicity* Checkpoint Kinase 1 Comet Assay DNA Breaks, Double-Stranded / drug effects* DNA Helicases / genetics DNA Helicases / metabolism* DNA Repair* Mutagenesis Protein Kinases / chemistry Protein Kinases / genetics Protein Kinases / metabolism RNA Interference Replication Protein A / antagonists & inhibitors Replication Protein A / genetics Replication Protein A / metabolism S Phase Cell Cycle Checkpoints / drug effects
IF 3.968
Times Cited 4
C.elegans tm1145