Anna Wood

In meiotic prophase I, hundreds of DNA double-strand breaks (DSBs) are formed throughout the genome. A majority of these breaks are repaired as non-crossovers (NCOs), while a minor subset are repaired as crossovers (CO). COs are essential for the first meiotic division, and errors in their formation can result in aneuploidy, germ cell death, birth defects, or infertility. These errors are more pronounced in female meiosis compared to males, indicating that the processes of CO formation, placement, resolution, and surveillance are sexually dimorphic. This study demonstrates a novel and dual roles for Cyclin N-Terminal Domain Containing 1 (CNTD1) in ensuring appropriate CO and synapsis between homologous chromosomes in oocytes. CNTD1-deficient oocytes fail to form COs and exhibit an exhausted follicle pool starting shortly after birth, which is dependent on CHK2, and temporally distinct from previously reported CO mutants. Further investigation into the CHK2-dependent follicle loss reveals that this is due to inappropriate retention of HORMAD1 and the absence of SKP1. Thus, in females, loss of Cntd1 appears to result in phenotypes that are temporally disconnected from known early and late CO mutants. These findings suggest that CNTD1 has novel roles beyond CO designation, particularly in regulating prophase I progression.

Replication Factor C like complexes (RLCs) are essential for DNA damage replication and repair in somatic cells. While their functions in mitotic cells have been extensively investigated, the role of RLCs in meiosis have remained largely unexplored. In meiosis, hundreds of pre-programmed double-strand breaks are formed between homologous chromosomes. Many of these breaks are repaired as non-crossovers; however, a minor population are repaired as crossovers, ensuring genetic diversity, but more importantly, faithful chromosome tethering through the first meiotic division. The selection of these sites are highly regulated by a cohort of pro-crossover proteins. In vitro evidence has emerged supporting the essential nature of RFC1-RLC and PCNA to facilitate the activity of the pro-crossover heterodimer MutL. Moreover IP-mass spectrometry data has shown the ability of RLCs to complex with the crossover associated protein, CNTD1 in mouse spermatogenesis. This first glimpse into the function of RLCs in context of meiosis has thus raised many questions pertaining to the function of how RLCs facilitate crossover designation and synapsis between homologous chromosomes.