RRC ID 46731
Author Lee SJ, Gartner A, Hyun M, Ahn B, Koo HS.
Title The Caenorhabditis elegans Werner syndrome protein functions upstream of ATR and ATM in response to DNA replication inhibition and double-strand DNA breaks.
Journal PLoS Genet
Abstract WRN-1 is the Caenorhabditis elegans homolog of the human Werner syndrome protein, a RecQ helicase, mutations of which are associated with premature aging and increased genome instability. Relatively little is known as to how WRN-1 functions in DNA repair and DNA damage signaling. Here, we take advantage of the genetic and cytological approaches in C. elegans to dissect the epistatic relationship of WRN-1 in various DNA damage checkpoint pathways. We found that WRN-1 is required for CHK1 phosphorylation induced by DNA replication inhibition, but not by UV radiation. Furthermore, WRN-1 influences the RPA-1 focus formation, suggesting that WRN-1 functions in the same step or upstream of RPA-1 in the DNA replication checkpoint pathway. In response to ionizing radiation, RPA-1 focus formation and nuclear localization of ATM depend on WRN-1 and MRE-11. We conclude that C. elegans WRN-1 participates in the initial stages of checkpoint activation induced by DNA replication inhibition and ionizing radiation. These functions of WRN-1 in upstream DNA damage signaling are likely to be conserved, but might be cryptic in human systems due to functional redundancy.
Volume 6(1)
Pages e1000801
Published 2010-1-1
DOI 10.1371/journal.pgen.1000801
PMID 20062519
PMC PMC2791846
MeSH Animals Ataxia Telangiectasia Mutated Proteins Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / radiation effects Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Checkpoint Kinase 1 DNA Breaks, Double-Stranded* / radiation effects DNA Helicases / genetics DNA Helicases / metabolism* DNA Repair DNA Replication* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Disease Models, Animal Down-Regulation Drosophila Proteins / genetics Drosophila Proteins / metabolism* Gamma Rays Humans Protein Kinases / genetics Protein Kinases / metabolism Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Replication Protein A / genetics Replication Protein A / metabolism Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* Ultraviolet Rays Werner Syndrome / genetics Werner Syndrome / metabolism*
IF 5.175
Times Cited 37
C.elegans tm764 tm853