title: The 53BP1 homolog in C. elegans influences DNA repair and promotes apoptosis in response to ionizing radiation.
abstract: 53BP1 contributes to activation of the G2/M checkpoint downstream of ATM and MDC1 in response to ionizing radiation and promotes nonhomologous end-joining (NHEJ) in mammalian cells. In order to determine whether the cellular activities of 53BP1 are conserved in the model organism C. elegans, we analyzed the function of its homolog, HSR-9 in response to DNA damage. Deletion or Mos1-insertion in hsr-9 did not affect the sensitivity of worms to double strand DNA breaks (DSBs), as reflected in embryonic survival and larval development. Nevertheless, the hsr-9 mutations, as well as a lig-4 deletion, reversed the hypersensitivity of rad-54-deficient worms to DSBs. In addition, oocyte chromosomal aberrations, which were increased by rad-54 knockdown in response to DSBs, were also reduced by the hsr-9 mutations. The hsr-9 mutations did not prevent the cell cycle arrest induced by DSBs in mitotically proliferating germ cells. However, they attenuated apoptosis induced by DSBs, but not when CEP-1 (a p53 ortholog) was absent, suggesting that HSR-9 functions in the same pathway as CEP-1. We concluded that the 53BP1 homolog in C. elegans is not directly involved in cell cycle arrest in response to DSBs, but that it promotes apoptosis and also a form of NHEJ that occurs only when rad-54 is deficient.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Ryu
authors.forename: Sang Jo
authors.initials: SJ
authors.lastname: Kang
authors.forename: Hyeon-Sook
authors.initials: HS
authors.lastname: Koo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D019295:Computational Biology; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D005720:Gamma Rays; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; C585045:HSR-9 protein, C elegans; D009687:Nuclear Proteins; D004265:DNA Helicases