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 recombination. In C. elegans, recombination between homologs is essential for proper segregation during anaphase I. The steps of recombination occur as follows: 1. SPO-11 introduces DNA double-strand breaks (1), 2. RAD-51-dependent single-end strand invasion favors repair from homologous chromosomes (4,5), and 3. crossover(CO) -specific DNA repair is promoted by MSH-4, MSH-5 and ZHP-3 (2,3). 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. Further, these factors appear to be required for initiation of the DNA-damage checkpoint since apoptosis decreases in
msh-4,
msh-5, and
zhp-3 mutants after IR radiation (6). We present an alternate explanation of these results: When we mutate a conserved upstream regulatory region of
egl-1,
msh-5 and
zhp-3 mutants now exhibit an increase in apoptosis and this increase is dependent on the DNA damage checkpoint protein HUS-1. We hypothesize that when CO recombination is specifically disrupted, DNA damage induced apoptosis is inhibited, potentially to promote repair over removal. We plan to 1) identify the regulatory factor(s) that bind EGL-1's regulatory region to limit apoptosis when CO recombination is defective and 2) test whether this inhibition of apoptosis is mechanistically linked to characterized meiotic feedback mechanisms that are activated by defects in recombination.