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Condensin II resolves chromosomal associations to enable anaphase I segregation in Drosophila male meiosis.

Hartl TA, Sweeney SJ, Knepler PJ, Bosco G - PLoS Genet. (2008)

Bottom Line: These persistent chromosome associations likely consist of DNA entanglements, but may be more specific as anaphase I bridging was rescued by mutations in the homolog conjunction factor teflon.We propose that the consequence of condensin II mutations is a failure to resolve heterologous and homologous associations mediated by entangled DNA and/or homolog conjunction factors.Furthermore, persistence of homologous and heterologous interchromosomal associations lead to anaphase I chromatin bridging and the generation of aneuploid gametes.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, United States of America.

ABSTRACT
Several meiotic processes ensure faithful chromosome segregation to create haploid gametes. Errors to any one of these processes can lead to zygotic aneuploidy with the potential for developmental abnormalities. During prophase I of Drosophila male meiosis, each bivalent condenses and becomes sequestered into discrete chromosome territories. Here, we demonstrate that two predicted condensin II subunits, Cap-H2 and Cap-D3, are required to promote territory formation. In mutants of either subunit, territory formation fails and chromatin is dispersed throughout the nucleus. Anaphase I is also abnormal in Cap-H2 mutants as chromatin bridges are found between segregating heterologous and homologous chromosomes. Aneuploid sperm may be generated from these defects as they occur at an elevated frequency and are genotypically consistent with anaphase I segregation defects. We propose that condensin II-mediated prophase I territory formation prevents and/or resolves heterologous chromosomal associations to alleviate their potential interference in anaphase I segregation. Furthermore, condensin II-catalyzed prophase I chromosome condensation may be necessary to resolve associations between paired homologous chromosomes of each bivalent. These persistent chromosome associations likely consist of DNA entanglements, but may be more specific as anaphase I bridging was rescued by mutations in the homolog conjunction factor teflon. We propose that the consequence of condensin II mutations is a failure to resolve heterologous and homologous associations mediated by entangled DNA and/or homolog conjunction factors. Furthermore, persistence of homologous and heterologous interchromosomal associations lead to anaphase I chromatin bridging and the generation of aneuploid gametes.

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Cap-H2 mutants are defective in anaphase II segregation.Metaphase II and anaphase II morphologies were compared between wild-type and Cap-H2Z3-0019/Cap-H2TH1 mutant males. Testes were stained with DAPI and an anti-tubulin antibody to visualize DNA (white) and microtubules (green), respectively (scale bar in 6A indicates 10 µm). (A) Wild-type metaphase/anaphase II cyst. Metaphase II cells are those where each bivalent has congressed to the metaphase plate and appear as a cluster of DAPI staining material. Anaphase II are those cells with two DAPI staining white clusters, indicating homologous chromosome segregation. (B) Metaphase II and anaphase II figures from a Cap-H2 strong mutant. Arrow indicates an anaphase II bridge. The arrowhead highlights an anaphase II bridge or lagging chromosome.
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pgen-1000228-g006: Cap-H2 mutants are defective in anaphase II segregation.Metaphase II and anaphase II morphologies were compared between wild-type and Cap-H2Z3-0019/Cap-H2TH1 mutant males. Testes were stained with DAPI and an anti-tubulin antibody to visualize DNA (white) and microtubules (green), respectively (scale bar in 6A indicates 10 µm). (A) Wild-type metaphase/anaphase II cyst. Metaphase II cells are those where each bivalent has congressed to the metaphase plate and appear as a cluster of DAPI staining material. Anaphase II are those cells with two DAPI staining white clusters, indicating homologous chromosome segregation. (B) Metaphase II and anaphase II figures from a Cap-H2 strong mutant. Arrow indicates an anaphase II bridge. The arrowhead highlights an anaphase II bridge or lagging chromosome.

Mentions: While the prevalence of meiotic anaphase I bridging is likely a major contributor to the observed 2nd and 3rd nondisjunction, it cannot be ruled out that the preceding stem cell and gonial mitotic divisions are also defective and lead to aneuploid sperm. This exists as a formal possibility, yet aneuploid meiotic I cells were not observed in squashed Cap-H2 mutant anaphase I figures where all chromosomes could be distinguished (n = 10). This suggests that pre-meiotic segregation is unaffected. Similarly, anaphase II defects could have contributed to the elevated o-2 and o-3 sperm and perhaps the slight increase in bw1/bw1 progeny that would have been generated from meiosis II nondisjunction (Table 3). In fact, anaphase II bridging was observed in 8.7% of Cap-H2Z3-0019/Cap-H2TH1 anaphase II figures (n = 69, Figure 6), 2.1% of those from Cap-H2Z3-0019/Cap-H2Z3-5163 males (n = 47), and never in the wild-type (n = 66). Anaphase II defects may occur because of a specific role of Cap-H2 in meiosis II, or alternatively, anaphase II bridging could be attributed to faulty chromosome assembly or individualization in meiosis I.


Condensin II resolves chromosomal associations to enable anaphase I segregation in Drosophila male meiosis.

Hartl TA, Sweeney SJ, Knepler PJ, Bosco G - PLoS Genet. (2008)

Cap-H2 mutants are defective in anaphase II segregation.Metaphase II and anaphase II morphologies were compared between wild-type and Cap-H2Z3-0019/Cap-H2TH1 mutant males. Testes were stained with DAPI and an anti-tubulin antibody to visualize DNA (white) and microtubules (green), respectively (scale bar in 6A indicates 10 µm). (A) Wild-type metaphase/anaphase II cyst. Metaphase II cells are those where each bivalent has congressed to the metaphase plate and appear as a cluster of DAPI staining material. Anaphase II are those cells with two DAPI staining white clusters, indicating homologous chromosome segregation. (B) Metaphase II and anaphase II figures from a Cap-H2 strong mutant. Arrow indicates an anaphase II bridge. The arrowhead highlights an anaphase II bridge or lagging chromosome.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2562520&req=5

pgen-1000228-g006: Cap-H2 mutants are defective in anaphase II segregation.Metaphase II and anaphase II morphologies were compared between wild-type and Cap-H2Z3-0019/Cap-H2TH1 mutant males. Testes were stained with DAPI and an anti-tubulin antibody to visualize DNA (white) and microtubules (green), respectively (scale bar in 6A indicates 10 µm). (A) Wild-type metaphase/anaphase II cyst. Metaphase II cells are those where each bivalent has congressed to the metaphase plate and appear as a cluster of DAPI staining material. Anaphase II are those cells with two DAPI staining white clusters, indicating homologous chromosome segregation. (B) Metaphase II and anaphase II figures from a Cap-H2 strong mutant. Arrow indicates an anaphase II bridge. The arrowhead highlights an anaphase II bridge or lagging chromosome.
Mentions: While the prevalence of meiotic anaphase I bridging is likely a major contributor to the observed 2nd and 3rd nondisjunction, it cannot be ruled out that the preceding stem cell and gonial mitotic divisions are also defective and lead to aneuploid sperm. This exists as a formal possibility, yet aneuploid meiotic I cells were not observed in squashed Cap-H2 mutant anaphase I figures where all chromosomes could be distinguished (n = 10). This suggests that pre-meiotic segregation is unaffected. Similarly, anaphase II defects could have contributed to the elevated o-2 and o-3 sperm and perhaps the slight increase in bw1/bw1 progeny that would have been generated from meiosis II nondisjunction (Table 3). In fact, anaphase II bridging was observed in 8.7% of Cap-H2Z3-0019/Cap-H2TH1 anaphase II figures (n = 69, Figure 6), 2.1% of those from Cap-H2Z3-0019/Cap-H2Z3-5163 males (n = 47), and never in the wild-type (n = 66). Anaphase II defects may occur because of a specific role of Cap-H2 in meiosis II, or alternatively, anaphase II bridging could be attributed to faulty chromosome assembly or individualization in meiosis I.

Bottom Line: These persistent chromosome associations likely consist of DNA entanglements, but may be more specific as anaphase I bridging was rescued by mutations in the homolog conjunction factor teflon.We propose that the consequence of condensin II mutations is a failure to resolve heterologous and homologous associations mediated by entangled DNA and/or homolog conjunction factors.Furthermore, persistence of homologous and heterologous interchromosomal associations lead to anaphase I chromatin bridging and the generation of aneuploid gametes.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, United States of America.

ABSTRACT
Several meiotic processes ensure faithful chromosome segregation to create haploid gametes. Errors to any one of these processes can lead to zygotic aneuploidy with the potential for developmental abnormalities. During prophase I of Drosophila male meiosis, each bivalent condenses and becomes sequestered into discrete chromosome territories. Here, we demonstrate that two predicted condensin II subunits, Cap-H2 and Cap-D3, are required to promote territory formation. In mutants of either subunit, territory formation fails and chromatin is dispersed throughout the nucleus. Anaphase I is also abnormal in Cap-H2 mutants as chromatin bridges are found between segregating heterologous and homologous chromosomes. Aneuploid sperm may be generated from these defects as they occur at an elevated frequency and are genotypically consistent with anaphase I segregation defects. We propose that condensin II-mediated prophase I territory formation prevents and/or resolves heterologous chromosomal associations to alleviate their potential interference in anaphase I segregation. Furthermore, condensin II-catalyzed prophase I chromosome condensation may be necessary to resolve associations between paired homologous chromosomes of each bivalent. These persistent chromosome associations likely consist of DNA entanglements, but may be more specific as anaphase I bridging was rescued by mutations in the homolog conjunction factor teflon. We propose that the consequence of condensin II mutations is a failure to resolve heterologous and homologous associations mediated by entangled DNA and/or homolog conjunction factors. Furthermore, persistence of homologous and heterologous interchromosomal associations lead to anaphase I chromatin bridging and the generation of aneuploid gametes.

Show MeSH
Related in: MedlinePlus