The germ line efficiently combats numerous genotoxic insults to ensure the high fidelity propagation of unaltered genomic information across generations. Yet, germ cells in most metazoans also intentionally create double-strand breaks (DSBs) to promote DNA exchange between parental chromosomes, a process known as crossing over. Homologous recombination is employed in the repair of both genotoxic lesions and programmed DSBs and many of the core DNA repair proteins function in both processes. In addition, DNA repair efficiency and crossover distribution are both influenced by local and global differences in chromatin structure, yet the interplay between chromatin structure, genome integrity, and meiotic fidelity is still poorly understand. We have used the
xnd-1 mutant of C. elegans to explore the relationship between genome integrity and crossover (CO) formation. Known for its role in ensuring X chromosome CO formation and germline development, we show that
xnd-1 also regulates genome stability.
xnd-1 mutants exhibited a mortal germ line, high embryonic lethality, high incidence of males, and sensitivity to ionizing radiation. We discovered that a hypomorphic allele of
mys-1 suppressed these genome instability phenotypes of
xnd-1 but did not suppress the CO defects, suggesting it serves as a separation-of-function allele.
mys-1 encodes the histone acetyltransferase whose homolog Tip60 acetylates H2AK5, a histone mark associated with transcriptional activation that is increased in
xnd-1 mutant germlines, raising the possibility that thresholds of H2AK5ac may differentially influence distinct germ line repair events. We also show that
xnd-1 regulated
him-5 transcriptionally, independently of
mys-1, and that ectopic expression of
him-5 suppressed the CO defects of
xnd-1 Our work provides
xnd-1 as a model in which to study the link between chromatin factors, gene expression, and genome stability.