title: Mouse HORMAD1 is a meiosis i checkpoint protein that modulates DNA double- strand break repair during female meiosis.
abstract: Oocytes in embryonic ovaries enter meiosis I and arrest in the diplonema stage. Perturbations in meiosis I, such as abnormal double-strand break (DSB) formation and repair, adversely affect oocyte survival. We previously discovered that HORMAD1 is a critical component of the synaptonemal complex but not essential for oocyte survival. No significant differences were observed in the number of primordial, primary, secondary, and developing follicles between wild-type and Hormad1(−/−)newborn, 8-day, and 80-day ovaries. Meiosis I progression in Hormad1(−/−) embryonic ovaries was normal through the zygotene stage and in oocytes arrested in diplonema; however, we did not visualize oocytes with completely synapsed chromosomes. We investigated effects of HORMAD1 deficiency on the kinetics of DNA DSB formation and repair in the mouse ovary. We irradiated Embryonic Day 16.5 wild-type and Hormad1(−/−) ovaries and monitored DSB repair using gammaH2AX, RAD51, and DMC1 immunofluorescence. Our results showed a significant drop in unrepaired DSBs in the irradiated Hormad1(−/−) zygotene oocytes as compared to the wild-type oocytes. Moreover, Hormad1 deficiency rescued Dmc1(−/−) oocytes. These results indicate that Hormad1 deficiency promotes DMC1-independent DSB repairs, which in turn helps asynaptic Hormad1(−/−) oocytes resist perinatal loss.
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Yong-Hyun
authors.initials: YH
authors.lastname: Shin
authors.forename: Megan M
authors.initials: MM
authors.lastname: McGuire
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Rajkovic
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C506693:Nohma protein, mouse