The 53BP1 Homolog in C. elegans Influences DNA Repair and Promotes Apoptosis in Response to Ionizing Radiation

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.