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C. elegans CEP-1/p53 and BEC-1 are involved in DNA repair.
PLoS One. 2014; 9(2):e88828.Plos

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+Show Affiliations

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.Department of Biological Sciences, Hunter College, City University of New York, New York City, New York, United States of America.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.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24586407

Citation

Hoffman, Sandy, et al. "C. Elegans CEP-1/p53 and BEC-1 Are Involved in DNA Repair." PloS One, vol. 9, no. 2, 2014, pp. e88828.
Hoffman S, Martin D, Meléndez A, et al. C. elegans CEP-1/p53 and BEC-1 are involved in DNA repair. PLoS One. 2014;9(2):e88828.
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. https://doi.org/10.1371/journal.pone.0088828
Hoffman S, et al. C. Elegans CEP-1/p53 and BEC-1 Are Involved in DNA Repair. PLoS One. 2014;9(2):e88828. PubMed PMID: 24586407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - C. elegans CEP-1/p53 and BEC-1 are involved in DNA repair. AU - Hoffman,Sandy, AU - Martin,Daniel, AU - Meléndez,Alicia, AU - Bargonetti,Jill, Y1 - 2014/02/20/ PY - 2013/10/31/received PY - 2014/01/10/accepted PY - 2014/3/4/entrez PY - 2014/3/4/pubmed PY - 2015/1/3/medline SP - e88828 EP - e88828 JF - PloS one JO - PLoS One VL - 9 IS - 2 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24586407/C__elegans_CEP_1/p53_and_BEC_1_are_involved_in_DNA_repair_ DB - PRIME DP - Unbound Medicine ER -