Reference - Detail
|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.|
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.
|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*|
|WOS Category||GENETICS & HEREDITY|