Mutations in Caenorhabditis elegans him-19 show meiotic defects that worsen with age.
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.
Tang
Lois
L
Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria.
Machacek
Thomas
T
Mamnun
Yasmine M
YM
Penkner
Alexandra
A
Gloggnitzer
Jiradet
J
Wegrostek
Christina
C
Konrat
Robert
R
Jantsch
Michael F
MF
Loidl
Josef
J
Jantsch
Verena
V
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D023902:Chromosome Pairing / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006066:Gonads / Q000033:anatomy & histology; D006801:Humans; D008297:Male; D008540:Meiosis / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D009866:Oogenesis / Q000502:physiology; D010641:Phenotype; D012326:RNA Splicing; D011995:Recombination, Genetic
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C551926:HIM-19 protein, C elegans