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

Tang L, Machacek T, Mamnun YM, Penkner A, Gloggnitzer J, Wegrostek C, Konrat R, Jantsch MF, Loidl J, Jantsch V - Mol. Biol. Cell (2010)

Bottom Line: Mutant him-19(jf6) animals show a reduction in pairing of homologous chromosomes and subsequent bivalent formation.Ultimately, mutation of him-19 leads to chromosome missegregation and reduced offspring viability.Further characterization of him-19 could contribute to our understanding of age-dependent meiotic defects in humans.

View Article: PubMed Central - PubMed

Affiliation: Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria.

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.

Show MeSH

Related in: MedlinePlus

Lateral HIM-3, and central SYP-1, components of the SC, are loaded in him-19(jf6). Spread pachytene nuclei were stained with an antibody against HIM-3 an axial element component of the SC. Loading of HIM3 occurs at the same time in wild-type and him-19(jf6) individuals. However, more HIM-3 tracks can be observed in the mutant (small arrowhead). Similarly, the central element component SYP-1 is loaded along the entire chromosome axes in wild-type nuclei (indicated by arrows). In him-19 (jf6), the extent of SYP-1 polymerization is reduced as demonstrated by the relatively short SYP-1 stretches (see arrowheads). Also, compare Supplemental Figure 5 for a more detailed view of SYP-1 loading. Bars, 10 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2836969&req=5

Figure 5: Lateral HIM-3, and central SYP-1, components of the SC, are loaded in him-19(jf6). Spread pachytene nuclei were stained with an antibody against HIM-3 an axial element component of the SC. Loading of HIM3 occurs at the same time in wild-type and him-19(jf6) individuals. However, more HIM-3 tracks can be observed in the mutant (small arrowhead). Similarly, the central element component SYP-1 is loaded along the entire chromosome axes in wild-type nuclei (indicated by arrows). In him-19 (jf6), the extent of SYP-1 polymerization is reduced as demonstrated by the relatively short SYP-1 stretches (see arrowheads). Also, compare Supplemental Figure 5 for a more detailed view of SYP-1 loading. Bars, 10 μm.

Mentions: In wild-type pachytene, when all chromosomes are properly paired and synapsed, six HIM-3 tracks and six SYP-1 tracks can be observed (see arrows in Figure 5). Moreover, DAPI staining revealed parallel chromatin tracks. In him-19(jf6) HIM-3 is polymerized along the chromosomes with wild-type kinetics (Figure 5). However, stainings seem less prominent and more HIM-3 tracks are discernible per cell most likely reflecting unpaired homologues (small arrowhead in Figure 5). Consistent with the reduced number of parallel tracks observed by DAPI staining, SYP-1 polymerized in a restricted manner (arrowheads in Figures 5 and 7A). Only short stretches of SYP-1 were seen upon entry into meiosis. From midpachytene onward, SYP-1 stretches polymerized more extensively. Finally, in late pachytene, SYP-1 polymerization reached its maximum (Figure 7). The SYP-1 loading pattern in him-19(jf6) is similar to the one observed in mutants of the meiotic regulator chk-2 (Martinez-Perez and Villeneuve, 2005). Because FISH demonstrated that most homologous regions are unpaired (see above), the extensive synapsis might involve nonhomologous partners. Consistently, partial SYP-1 tracks can frequently be found between DAPI-positive structures, suggesting fragmentary polymerization between paired chromosomes (see arrow in Supplemental Figure 5A). SYP-1 might also polymerize along unpaired chromosomes as described for cra-1 mutants (Smolikov et al., 2008). Regardless, immuno-FISH experiments and stainings with HIM-8 revealed that the partial SYP-1 stretches are formed along/between nonhomologous chromosomes (Figure 4, B and C, and Supplemental Figure 5B).


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

Tang L, Machacek T, Mamnun YM, Penkner A, Gloggnitzer J, Wegrostek C, Konrat R, Jantsch MF, Loidl J, Jantsch V - Mol. Biol. Cell (2010)

Lateral HIM-3, and central SYP-1, components of the SC, are loaded in him-19(jf6). Spread pachytene nuclei were stained with an antibody against HIM-3 an axial element component of the SC. Loading of HIM3 occurs at the same time in wild-type and him-19(jf6) individuals. However, more HIM-3 tracks can be observed in the mutant (small arrowhead). Similarly, the central element component SYP-1 is loaded along the entire chromosome axes in wild-type nuclei (indicated by arrows). In him-19 (jf6), the extent of SYP-1 polymerization is reduced as demonstrated by the relatively short SYP-1 stretches (see arrowheads). Also, compare Supplemental Figure 5 for a more detailed view of SYP-1 loading. Bars, 10 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2836969&req=5

Figure 5: Lateral HIM-3, and central SYP-1, components of the SC, are loaded in him-19(jf6). Spread pachytene nuclei were stained with an antibody against HIM-3 an axial element component of the SC. Loading of HIM3 occurs at the same time in wild-type and him-19(jf6) individuals. However, more HIM-3 tracks can be observed in the mutant (small arrowhead). Similarly, the central element component SYP-1 is loaded along the entire chromosome axes in wild-type nuclei (indicated by arrows). In him-19 (jf6), the extent of SYP-1 polymerization is reduced as demonstrated by the relatively short SYP-1 stretches (see arrowheads). Also, compare Supplemental Figure 5 for a more detailed view of SYP-1 loading. Bars, 10 μm.
Mentions: In wild-type pachytene, when all chromosomes are properly paired and synapsed, six HIM-3 tracks and six SYP-1 tracks can be observed (see arrows in Figure 5). Moreover, DAPI staining revealed parallel chromatin tracks. In him-19(jf6) HIM-3 is polymerized along the chromosomes with wild-type kinetics (Figure 5). However, stainings seem less prominent and more HIM-3 tracks are discernible per cell most likely reflecting unpaired homologues (small arrowhead in Figure 5). Consistent with the reduced number of parallel tracks observed by DAPI staining, SYP-1 polymerized in a restricted manner (arrowheads in Figures 5 and 7A). Only short stretches of SYP-1 were seen upon entry into meiosis. From midpachytene onward, SYP-1 stretches polymerized more extensively. Finally, in late pachytene, SYP-1 polymerization reached its maximum (Figure 7). The SYP-1 loading pattern in him-19(jf6) is similar to the one observed in mutants of the meiotic regulator chk-2 (Martinez-Perez and Villeneuve, 2005). Because FISH demonstrated that most homologous regions are unpaired (see above), the extensive synapsis might involve nonhomologous partners. Consistently, partial SYP-1 tracks can frequently be found between DAPI-positive structures, suggesting fragmentary polymerization between paired chromosomes (see arrow in Supplemental Figure 5A). SYP-1 might also polymerize along unpaired chromosomes as described for cra-1 mutants (Smolikov et al., 2008). Regardless, immuno-FISH experiments and stainings with HIM-8 revealed that the partial SYP-1 stretches are formed along/between nonhomologous chromosomes (Figure 4, B and C, and Supplemental Figure 5B).

Bottom Line: Mutant him-19(jf6) animals show a reduction in pairing of homologous chromosomes and subsequent bivalent formation.Ultimately, mutation of him-19 leads to chromosome missegregation and reduced offspring viability.Further characterization of him-19 could contribute to our understanding of age-dependent meiotic defects in humans.

View Article: PubMed Central - PubMed

Affiliation: Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria.

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.

Show MeSH
Related in: MedlinePlus