C. elegans CEP-1/p53 and BEC-1 Are Involved in DNA Repair

Sandy Hoffman, Daniel Martin, Alicia Meléndez, Jill Bargonetti, Peiwen Fei
2014 PLoS ONE  
p53 is a transcription factor that regulates the response to cellular stress. Mammalian p53 functions as a tumor suppressor. The C. elegans p53, cep-1, regulates DNA-damage induced germline cell death by activating the transcription of egl-1 and ced-13. We used the C. elegans model to investigate how, in the whole animal, different forms of DNA damage can induce p53-dependent versus p53-independent cell death and DNA repair. DNA damage was induced by ultraviolet type C (UVC) radiation, or
more » ... arbamoyl mitomycin C (DMC, an agent known to induce mammalian p53-independent cell death). Wildtype or cep-1 loss-of-function mutant animals were assayed for germline cell death and DNA lesions. Wild-type animals displayed greater removal of UVC-lesions over time, whereas cep-1 mutant animals displayed increased UVC-lesion retention. The cep-1 mutation increased UVC-lesion retention directly correlated with a reduction of progeny viability. Consistent with DMC inducing p53-independent cell death in mammalian cells DMC induced a C. elegans p53-independent germline cell death pathway. To examine the influence of wild-type CEP-1 and DNA damage on C. elegans tumors we used glp-1(ar202gf)/Notch germline tumor mutants. UVC treatment of glp-1 mutant animals activated the CEP-1 target gene egl-1 and reduced tumor size. In cep-1(gk138);glp-1(ar202gf) animals, UVC treatment resulted in increased susceptibility to lesions and larger tumorous germlines. Interestingly, the partial knockdown of bec-1 in adults resulted in a CEP-1-dependent increase in germline cell death and an increase in DNA damage. These results strongly support cross-talk between BEC-1 and CEP-1 to protect the C. elegans genome. Citation: Hoffman S, Martin D, Meléndez A, Bargonetti J (2014) C. elegans CEP-1/p53 and BEC-1 Are Involved in DNA Repair. PLoS ONE 9(2): e88828.
doi:10.1371/journal.pone.0088828 pmid:24586407 pmcid:PMC3930633 fatcat:tqz5r6neq5gavhkjgs3bvevcum