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. Copyright © 2005, American Society for Microbiology. All Rights Reserved. |
Keywords: |
unclassified drug; mutation; nonhuman; animal cell; mouse; spermatocyte; cytology; meiosis; animals; mice; spermatocytes; animal tissue; dna repair; apoptosis; protein; mice, inbred c57bl; time factors; mice, transgenic; dna strand breakage; molecular marker; gene expression regulation, developmental; double stranded dna; genetic recombination; chromatin; recombination, genetic; atm protein; microscopy, fluorescence; models, genetic; chromosome protein; testis; developmental stage; mutant; spo11 protein; fluorescent antibody technique, indirect; epistasis; sex chromosome; epistasis, genetic; seminiferous tubule; protein dmc1; protein topbp1
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