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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.
Original language | English |
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Article number | e1000801 |
Pages (from-to) | - |
Number of pages | 11 |
Journal | PLoS Genetics |
Volume | 6 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2010 |
Keywords
- C-ELEGANS
- DAMAGE CHECKPOINT
- INDUCED APOPTOSIS
- SYNDROME HELICASE
- RECQ HELICASE
- LIFE-SPAN
- S-PHASE
- EXONUCLEASE
- ACTIVATION
- PHOSPHORYLATION
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Dive into the research topics of 'The Caenorhabditis elegans Werner Syndrome Protein functions upstream of ATR and ATM in response to DNA Replication Inhibition and Double-Strand DNA Breaks'. Together they form a unique fingerprint.Projects
- 1 Finished
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Combined Genetic and Biochemical Approaches to Uncover and Characterize Redundant Factors Involved in Late Stages of Recombinational Repair
Gartner, A. (Investigator) & Lamond, A. (Investigator)
1/08/10 → 30/04/17
Project: Research