Meiotic Double-Strand Break Proteins Influence Repair Pathway Utilization

Abstract

Double-strand breaks (DSBs) are among the most deleterious lesions DNA can endure. Yet, DSBs are programmed at the onset of meiosis and are required to facilitate appropriate reduction of ploidy in daughter cells. Repair of these break is tightly controlled to favor homologous recombination (HR), the only repair pathway that can form crossovers.\n\nHowever, little is known about how the activities of alternative repair pathways are regulated at these stages. We discovered an unexpected synthetic interaction between the DSB machinery and strand-exchange proteins. Depleting the C. elegans DSB-promoting factors HIM-5 and DSB-2 suppresses the formation of chromosome fusions that arise in the absence of RAD-51 or other strand-exchange mediators. Our investigations reveal that non-homologous and theta-mediated end joining (c-NHEJ and TMEJ, respectively) and single strand annealing (SSA) function redundantly to repair DSBs when HR is compromised and that HIM-5 influences the utilization of TMEJ and SSA.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC=\"FIGDIR/small/376582_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (26K):\norg.highwire.dtl.DTLVardef@6e6a89org.highwire.dtl.DTLVardef@1145d1borg.highwire.dtl.DTLVardef@1eccd82org.highwire.dtl.DTLVardef@1a82e7d_HPS_FORMAT_FIGEXP M_FIG C_FIG