Ofer Rog: Regulating sister interactions during meiosis

The production of gametes during meiosis requires that the parental chromosomes (homologs) form physical linkages through the repair of DNA breaks by homologous recombination. Meiotic repair occurs within a dedicated chromosome organization where the two homologs, each consisting of two identical sister chromatids, are aligned side-by-side. Unlike in somatic cells where break repair is strongly biased towards the sister chromatid, meiotic repair is heavily biased towards using the homolog as a repair template. Despite its importance for the production of gametes, the mechanism that generates homolog bias remains unknown. To address the organization of sister chromatids within each homolog we used single-sister labeling in the C. elegans germline. We find that the sisters are well-separated (resolved) throughout the period when meiotic repair is taking place, and that sister resolution requires the cohesin loader NIPBL/SCC-2. Our findings suggest that the sisters may be as far away from one another as they are from the homolog, arguing against some of the models that have been proposed for the meiotic bias toward homolog-directed repair. Our insights into sister organization also inform our broader efforts to define the frequency, kinetics and regulation of various homolog- and sister-directed outcomes of meiotic break repair.