摘要：

Diversity in the animal kingdom is established through mutations, gene flow, and sexual reproduction. During gamete production, genetic material is exchanged between maternal and paternal chromosomes via a process called crossover (CO) recombination. In C. elegans, recombination between homologs is essential for proper segregation during anaphase I. During this process, double strand breaks are enzymatically induced via SPO-11 and repaired through the CO pathway. Thus, loss of CO promoting factors, such as MSH-4, MSH-5 and ZHP-3, should lead to persistent DNA damage and an increase in activation of DNA damage induced apoptosis, a process dependent on the conserved apoptosis activator, EGL-1. However, Silva et al showed that loss of these CO-promoting factors fails to activate DNA damage induced apoptosis (32). Further, these factors are hypothesized to be required for initiation of the DNA-damage checkpoint since apoptosis fails to activate in msh-4, msh-5, and zhp-3 mutants after IR radiation. We present an alternate explanation of these results: When a conserved upstream regulatory region of egl-1 is mutated, msh-5 and zhp-3 mutants exhibit an increase in apoptosis dependent on the DNA damage checkpoint proteins, HUS-1 and CEP-1. Also, a feedback mechanism involving PCH-2, a AAA+ ATPase that is activated by defects in recombination is not required for DDR dependent apoptotic regulation. This is in contrast to the requirement of PCH-2 for synaptic mutants to activate germline apoptosis. Based on these results, we hypothesized that when CO recombination is specifically disrupted, DNA damage induced apoptosis is inhibited, potentially to favor repair over removal. Our goal was to understand the regulation of apoptosis during the process of CO recombination and to identify a novel regulatory factor(s) that interacts with an egl-1 regulatory region (bc373) to limit apoptosis when CO recombination is defective. We tested a variety of factors including NHR-6, NHR-72, NHR-91, and screened 98 oogenic transcription factors.

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