Conditional Inactivation of the DNA Damage Response Gene Hus1 in Mouse Testis Reveals Separable Roles for Components of the RAD9-RAD1-HUS1 Complex in Meiotic Chromosome Maintenance

摘要: The RAD9-RAD1-HUS1 (9-1-1) complex is a heterotrimeric PCNA-like clamp that responds to DNA damage in somatic cells by promoting repair as well ATR-dependent checkpoint signaling. In yeast, worms, and flies, the 9-1-1 also required for meiotic function efficient completion of recombination; however, since Rad9, Rad1, Hus1 are essential genes mammals, little known about their functions mammalian germ cells. this study, we assessed analyzing mice with cell-specific deletion examining localization RAD9 RAD1 on chromosomes during prophase I. loss testicular resulted defects, cell depletion, severely compromised fertility. Hus1-deficient primary spermatocytes exhibited persistent autosomal γH2AX RAD51 staining indicative unrepaired DSBs, synapsis an extended XY body domain often encompassing partial or whole autosomes, increase structural chromosome abnormalities such end-to-end X chromosome-autosome fusions ruptures synaptonemal complex. Most these aberrations persisted diplotene-stage spermatocytes. Consistent role DSB repair, localized punctate, RAD51-containing foci Hus1-dependent manner. Interestingly, had broader distribution only partially overlapped RAD9, both ATR activator TOPBP1 unsynapsed autosomes was intact conditional knockouts. We conclude HUS1 acts component canonical I promote further propose respond chromatin through alternative mechanism does not require HUS1.