Regulation of DNA damage apoptosis in C. elegans meiosis

In the C. elegans germline, by the end of pachytene, about half of the oocytes nuclei undergo physiological cell death. In addition, apoptosis is triggered by DNA damage that can activate a specific checkpoint. Among the fundamental genes involved in the DNA damage checkpoint activation are hus-1, the p53 orthologue cep-1, and egl-1. We have shown that, the MSH-4, MSH-5 and ZHP-3 procrossover factors, that are necessary for crossover formation, are also required for DNA damage induced apoptosis. In fact, in the absence of these proteins, both DNA damage apoptosis induced by IR, or by failure in DNA repair due to mutations in genes, such as brc-1 or fcd-2, is abrogate (Adamo et al., 2008; Adamo et al., 2010; Silva et al., 2013). However elevated apoptosis enhancement in some other DNA repair mutants, such as rad-51 and him-6, is not suppressed by mutations in the above mentioned procrossover factors. We are investigating whether other key factors of meiosis, such as COM-1 (homolog of CtIP/Sae2/Ctp1) a crucial regulator of meiotic DSB repair pathway choice, may be necessary for damage dependent apoptosis in C. elegans. Although com-1 shows a role in damage dependent apoptosis after IR and in rad-51 background, it is not involved in the regulation of the apoptosis in DNA repair defective backgrounds such as him-6 (BLM homolog) and brc-1 both acting downstream during meiosis. We also investigate the role in apoptosis of another meiotic gene rmh-1 (a recQ elicases acting in complex with BLM and TOP3 at the level of Holliday junctions). rmh-1, such as com-1, shows a role in damage dependent apoptosis after IR and in him-6 background, but it is not involved in the regulation of the apoptosis in other DNA repair defective backgrounds such as brc-1 and cosa-1. We reasoned that there may be distinct apoptosis regulators at different steps of meiosis.