The Drosophila hus1 gene is required for homologous recombination repair during meiosis.
The checkpoint proteins, Rad9, Rad1, and Hus1 (9-1-1), form a complex which plays a central role in the DNA damage-induced checkpoint response. Previously, we demonstrated that Drosophilahus1 is essential for activation of the meiotic checkpoint elicited in double-strand DNA break (DSB) repair enzyme mutants. The hus1 mutant exhibits similar oocyte nuclear defects as those produced by mutations in these repair enzymes, suggesting that hus1 plays a role independent of its meiotic checkpoint activity. In this study, we further analyzed the function of hus1 during meiosis and discovered that the synaptonemal complex (SC) disassembles abnormally in hus1 mutants. Oocyte nuclear and SC defects of hus1 mutants can be suppressed by blocking the formation of DSBs, implying that the hus1 oocyte nuclear defects depend upon DSBs. Interestingly, eliminating checkpoint activity through mutations in DmChk2 but not mei-41 suppress the oocyte nucleus and SC defects of hus1, suggesting that these processes are dependent upon DmChk2 checkpoint activity. Moreover, we showed that in hus1, DSBs that form during meiosis are not processed efficiently, and that this defect is not suppressed by a mutation in DmChk2. We found a genetic interaction between hus1 and the Drosophila brca2 homologue, which was shown to participate in DNA repair during meiosis. Together, our results imply that hus1 is required for repair of DSBs during meiotic recombination.
Peretz
Gabriella
G
Department of Life Sciences and The National Institute for Biotechnology in the Negev, Ben-Gurion University, POB 653, Beer-Sheva 84105, Israel.
Arie
Lihi Gur
LG
Bakhrat
Anna
A
Abdu
Uri
U
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008540:Meiosis; D008954:Models, Biological; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D011995:Recombination, Genetic; D013573:Synaptonemal Complex / Q000378:metabolism
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C524443:Hus1-like protein, Drosophila