title: Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage.
abstract: Fundamentally different recombination defects cause apoptosis of mouse spermatocytes at the same stage in development, stage IV of the seminiferous epithelium cycle, equivalent to mid-pachynema in normal males. To understand the cellular response(s) that triggers apoptosis, we examined markers of spermatocyte development in mice with different recombination defects. In Spo11(-)(/)(-) mutants, which lack the double-strand breaks (DSBs) that initiate recombination, spermatocytes express markers of early to mid-pachynema, forming chromatin domains that contain sex body-associated proteins but that rarely encompass the sex chromosomes. Dmc1(-)(/)(-) spermatocytes, impaired in DSB repair, appear to arrest at or about late zygonema. Epistasis analysis reveals that this earlier arrest is a response to unrepaired DSBs, and cytological analysis implicates the BRCT-containing checkpoint protein TOPBP1. Atm(-)(/)(-) spermatocytes show similarities to Dmc1(-)(/)(-) spermatocytes, suggesting that ATM promotes meiotic DSB repair. Msh5(-)(/)(-) mutants display a set of characteristics distinct from these other mutants. Thus, despite equivalent stages of spermatocyte elimination, different recombination-defective mutants manifest distinct responses, providing insight into surveillance mechanisms in male meiosis.
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Barchi
authors.forename: Shantha
authors.initials: S
authors.lastname: Mahadevaiah
authors.forename: Monica
authors.initials: M
authors.lastname: Di Giacomo
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baudat
authors.forename: Dirk G
authors.initials: DG
authors.lastname: de Rooij
authors.forename: Paul S
authors.initials: PS
authors.lastname: Burgoyne
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.forename: Scott
authors.initials: S
authors.lastname: Keeney
mesh_terms: D000818:Animals; D017209:Apoptosis; D002843:Chromatin / Q000378:metabolism; D004260:DNA Repair; D004843:Epistasis, Genetic; D019084:Fluorescent Antibody Technique, Indirect; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009154:Mutation; D011995:Recombination, Genetic; D013090:Spermatocytes / Q000166:cytology* / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D013997:Time Factors
chemical_list: D002843:Chromatin