title: C. elegans CEP-1/p53 and BEC-1 are involved in DNA repair.
abstract: 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 10-decarbamoyl mitomycin C (DMC, an agent known to induce mammalian p53-independent cell death). Wild-type 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.
authors.affiliation: Department of Biological Sciences, Hunter College, City University of New York, New York City, New York, United States of America ; The Graduate Center Departments of Biology and Biochemistry, City University of New York, New York City, New York, United States of America.
authors.forename: Sandy
authors.initials: S
authors.lastname: Hoffman
authors.affiliation: Department of Biological Sciences, Hunter College, City University of New York, New York City, New York, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.affiliation: Department of Biological Sciences Queens College, City University of New York, Queens, New York, United States of America ; The Graduate Center Departments of Biology and Biochemistry, City University of New York, New York City, New York, United States of America.
authors.forename: Alicia
authors.initials: A
authors.lastname: Meléndez
authors.affiliation: Department of Biological Sciences, Hunter College, City University of New York, New York City, New York, United States of America ; The Graduate Center Departments of Biology and Biochemistry, City University of New York, New York City, New York, United States of America.
authors.forename: Jill
authors.initials: J
authors.lastname: Bargonetti
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004249:DNA Damage / Q000528:radiation effects; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics*; D005854:Germ Cells / Q000187:drug effects / Q000502:physiology; D008937:Mitomycins / Q000494:pharmacology; D034622:RNA Interference; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C504038:Ced-13 protein, C elegans; D017931:DNA Primers; C112486:EGL-1 protein, C elegans; D008937:Mitomycins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D033921:Vesicular Transport Proteins; C477268:bec-1 protein, C elegans; C067795:10-decarbamoylmitomycin C