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. Consist...

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Bibliographic Details
Published in:Molecular biology of the cell 2010-03, Vol.21 (6), p.885-896
Main Authors: Tang, Lois, Machacek, Thomas, Mamnun, Yasmine M, Penkner, Alexandra, Gloggnitzer, Jiradet, Wegrostek, Christina, Konrat, Robert, Jantsch, Michael F, Loidl, Josef, Jantsch, Verena
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Caenorhabditis elegans - anatomy & histology
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Chromosome Pairing - genetics
DNA Breaks, Double-Stranded
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Female
Gonads - anatomy & histology
Humans
Male
Meiosis - physiology
Molecular Sequence Data
Mutation
Oogenesis - physiology
Phenotype
Recombination, Genetic
RNA Splicing
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E09-09-0811