Mutations in Caenorhabditis elegans him-19 show meiotic defects that worsen with age

秀丽隐杆线虫 him-19 突变显示减数分裂缺陷,且会随着年龄增长而恶化

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作者:Lois Tang, Thomas Machacek, Yasmine M Mamnun, Alexandra Penkner, Jiradet Gloggnitzer, Christina Wegrostek, Robert Konrat, Michael F Jantsch, Josef Loidl, Verena Jantsch

Abstract

From a screen for meiotic Caenorhabditis elegans mutants based on high incidence of males, we identified a novel gene, him-19, with multiple functions in prophase of meiosis I. Mutant him-19(jf6) animals show a reduction in pairing of homologous chromosomes and subsequent bivalent formation. Consistently, synaptonemal complex formation is spatially restricted and possibly involves nonhomologous chromosomes. Also, foci of the recombination protein RAD-51 occur delayed or cease altogether. Ultimately, mutation of him-19 leads to chromosome missegregation and reduced offspring viability. The observed defects suggest that HIM-19 is important for both homology recognition and formation of meiotic DNA double-strand breaks. It therefore seems to be engaged in an early meiotic event, resembling in this respect the regulator kinase CHK-2. Most astonishingly, him-19(jf6) hermaphrodites display worsening of phenotypes with increasing age, whereas defects are more severe in female than in male meiosis. This finding is consistent with depletion of a him-19-dependent factor during the production of oocytes. Further characterization of him-19 could contribute to our understanding of age-dependent meiotic defects in humans.

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