The Caenorhabditis elegans Werner Syndrome Protein functions upstream of ATR and ATM in response to DNA Replication Inhibition and Double-Strand DNA Breaks

Se-Jin Lee, Anton Gartner, Moonjung Hyun, Byungchan Ahn, Hyeon-Sook Koo

    Research output: Contribution to journalArticlepeer-review

    42 Citations (Scopus)

    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 languageEnglish
    Article numbere1000801
    Pages (from-to)-
    Number of pages11
    JournalPLoS Genetics
    Volume6
    Issue number1
    DOIs
    Publication statusPublished - Jan 2010

    Keywords

    • C-ELEGANS
    • DAMAGE CHECKPOINT
    • INDUCED APOPTOSIS
    • SYNDROME HELICASE
    • RECQ HELICASE
    • LIFE-SPAN
    • S-PHASE
    • EXONUCLEASE
    • ACTIVATION
    • PHOSPHORYLATION

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