論文 - 詳細
RRC ID | 46731 |
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著者 | Lee SJ, Gartner A, Hyun M, Ahn B, Koo HS. |
タイトル | The Caenorhabditis elegans Werner syndrome protein functions upstream of ATR and ATM in response to DNA replication inhibition and double-strand DNA breaks. |
ジャーナル | 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. |
巻・号 | 6(1) |
ページ | e1000801 |
公開日 | 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 |
引用数 | 37 |
WOS 分野 | GENETICS & HEREDITY |
リソース情報 | |
線虫 | tm764 tm853 |