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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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Teflon mutations rescue the homologous and heterologous chromosomal associations of Cap-H2 mutants.(A) Chromatin bridges were not observed in wild-type anaphase I figures (n = 90), yet occur in Cap-H2 mutants in a manner directly related to allelic strength. Bridges occurred 11.5% of anaphase I figures from fertile Cap-H2Z3-0019/Cap-H2Z3-5163 males (n = 78) and in 30.4% of those from sterile Cap-H2Z3-0019/Cap-H2TH1 males (n = 102). Mutations in eflon suppress the anaphase I bridging of sterile Cap-H2 mutant males to 10.8% (n = 74, p<1×10−6, X2 test). (B) Chromatin bridges were not observed in squashed anaphase I figures from wild-type preparations (n = 14), yet occurred in 40.5% of anaphase I figures from Cap-H2Z3-0019/Cap-H2TH1 males (n = 42). Bridges where the chromosomal nature could not be determined constitute 19% of the anaphase I figures (as indicated by the gray portion of the bar graph). The remaining 21.4% appeared to be bridging that existed between homologous chromosomes (burgundy portion). Mutations in eflon suppressed overall anaphase I bridging in squashed preparations to 25.6% (n = 43, p<0.05, X2 test) and homologous chromosome bridging to 9.3% (p<0.1, X2 test). (C) Cap-H2Z3-0019/Cap-H2TH1 males have an elevated amount of meiosis I 4th-to-heterolog threads relative to wild-type and these are suppressible by teflon mutations. In prometaphase I to telophase I, 4th-to-heterolog threads occur in 19% of wild-type (n = 21), 42.5% in Cap-H2Z3-0019/Cap-H2TH1 (n = 40), and 6% in tefZ2-5549/tefZ2-5864; Cap-H2Z3-0019/Cap-H2TH1 (n = 50) squashed figures. The ability of teflon mutations to rescue Cap-H2 mutant 4th-to-heterolog threads was significant (p<0.00001, X2 test). (D) Bridged Cap-H2Z3-0019/Cap-H2TH1 anaphase I squashed figures. See also Figures 4 and 5. (A) Bridged tefZ2-5864/tefZ2-5549; Cap-H2Z3-0019/Cap-H2TH1 squashed anaphase I figures.
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pgen-1000228-g007: Teflon mutations rescue the homologous and heterologous chromosomal associations of Cap-H2 mutants.(A) Chromatin bridges were not observed in wild-type anaphase I figures (n = 90), yet occur in Cap-H2 mutants in a manner directly related to allelic strength. Bridges occurred 11.5% of anaphase I figures from fertile Cap-H2Z3-0019/Cap-H2Z3-5163 males (n = 78) and in 30.4% of those from sterile Cap-H2Z3-0019/Cap-H2TH1 males (n = 102). Mutations in eflon suppress the anaphase I bridging of sterile Cap-H2 mutant males to 10.8% (n = 74, p<1×10−6, X2 test). (B) Chromatin bridges were not observed in squashed anaphase I figures from wild-type preparations (n = 14), yet occurred in 40.5% of anaphase I figures from Cap-H2Z3-0019/Cap-H2TH1 males (n = 42). Bridges where the chromosomal nature could not be determined constitute 19% of the anaphase I figures (as indicated by the gray portion of the bar graph). The remaining 21.4% appeared to be bridging that existed between homologous chromosomes (burgundy portion). Mutations in eflon suppressed overall anaphase I bridging in squashed preparations to 25.6% (n = 43, p<0.05, X2 test) and homologous chromosome bridging to 9.3% (p<0.1, X2 test). (C) Cap-H2Z3-0019/Cap-H2TH1 males have an elevated amount of meiosis I 4th-to-heterolog threads relative to wild-type and these are suppressible by teflon mutations. In prometaphase I to telophase I, 4th-to-heterolog threads occur in 19% of wild-type (n = 21), 42.5% in Cap-H2Z3-0019/Cap-H2TH1 (n = 40), and 6% in tefZ2-5549/tefZ2-5864; Cap-H2Z3-0019/Cap-H2TH1 (n = 50) squashed figures. The ability of teflon mutations to rescue Cap-H2 mutant 4th-to-heterolog threads was significant (p<0.00001, X2 test). (D) Bridged Cap-H2Z3-0019/Cap-H2TH1 anaphase I squashed figures. See also Figures 4 and 5. (A) Bridged tefZ2-5864/tefZ2-5549; Cap-H2Z3-0019/Cap-H2TH1 squashed anaphase I figures.

Mentions: The protein Teflon is implicated in the maintenance of Drosophila male meiosis I autosome conjunction as teflon mutants lose autosomal associations prior to anaphase I [31]. To investigate whether persistent associations between homologous chromosomes in anaphase I of Cap-H2 mutants (Figure 4B and 4C) are Teflon dependent, teflon mutations were crossed into a Cap-H2 mutant background and the frequency of anaphase I bridging was assessed. While 30.4% of anaphase I figures from Cap-H2Z3-0019/Cap-H2TH1 males were bridged (n = 102), bridging existed within only 10.8% of anaphase I figures from tefZ2-5549/tefZ2-5864; Cap-H2Z3-0019/Cap-H2TH1 males (n = 74, p<1×10−6, X2) (Figure 7A). Furthermore, in squashed preparations anaphase I bridging was decreased from 40.5% in Cap-H2Z3-0019/Cap-H2TH1 males (n = 42) to 25.6% in the tefZ2-5549/tefZ2-5864; Cap-H2Z3-0019/Cap-H2TH1 double mutants (n = 43, p<0.05, X2).


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)

Teflon mutations rescue the homologous and heterologous chromosomal associations of Cap-H2 mutants.(A) Chromatin bridges were not observed in wild-type anaphase I figures (n = 90), yet occur in Cap-H2 mutants in a manner directly related to allelic strength. Bridges occurred 11.5% of anaphase I figures from fertile Cap-H2Z3-0019/Cap-H2Z3-5163 males (n = 78) and in 30.4% of those from sterile Cap-H2Z3-0019/Cap-H2TH1 males (n = 102). Mutations in eflon suppress the anaphase I bridging of sterile Cap-H2 mutant males to 10.8% (n = 74, p<1×10−6, X2 test). (B) Chromatin bridges were not observed in squashed anaphase I figures from wild-type preparations (n = 14), yet occurred in 40.5% of anaphase I figures from Cap-H2Z3-0019/Cap-H2TH1 males (n = 42). Bridges where the chromosomal nature could not be determined constitute 19% of the anaphase I figures (as indicated by the gray portion of the bar graph). The remaining 21.4% appeared to be bridging that existed between homologous chromosomes (burgundy portion). Mutations in eflon suppressed overall anaphase I bridging in squashed preparations to 25.6% (n = 43, p<0.05, X2 test) and homologous chromosome bridging to 9.3% (p<0.1, X2 test). (C) Cap-H2Z3-0019/Cap-H2TH1 males have an elevated amount of meiosis I 4th-to-heterolog threads relative to wild-type and these are suppressible by teflon mutations. In prometaphase I to telophase I, 4th-to-heterolog threads occur in 19% of wild-type (n = 21), 42.5% in Cap-H2Z3-0019/Cap-H2TH1 (n = 40), and 6% in tefZ2-5549/tefZ2-5864; Cap-H2Z3-0019/Cap-H2TH1 (n = 50) squashed figures. The ability of teflon mutations to rescue Cap-H2 mutant 4th-to-heterolog threads was significant (p<0.00001, X2 test). (D) Bridged Cap-H2Z3-0019/Cap-H2TH1 anaphase I squashed figures. See also Figures 4 and 5. (A) Bridged tefZ2-5864/tefZ2-5549; Cap-H2Z3-0019/Cap-H2TH1 squashed anaphase I figures.
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Related In: Results  -  Collection

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pgen-1000228-g007: Teflon mutations rescue the homologous and heterologous chromosomal associations of Cap-H2 mutants.(A) Chromatin bridges were not observed in wild-type anaphase I figures (n = 90), yet occur in Cap-H2 mutants in a manner directly related to allelic strength. Bridges occurred 11.5% of anaphase I figures from fertile Cap-H2Z3-0019/Cap-H2Z3-5163 males (n = 78) and in 30.4% of those from sterile Cap-H2Z3-0019/Cap-H2TH1 males (n = 102). Mutations in eflon suppress the anaphase I bridging of sterile Cap-H2 mutant males to 10.8% (n = 74, p<1×10−6, X2 test). (B) Chromatin bridges were not observed in squashed anaphase I figures from wild-type preparations (n = 14), yet occurred in 40.5% of anaphase I figures from Cap-H2Z3-0019/Cap-H2TH1 males (n = 42). Bridges where the chromosomal nature could not be determined constitute 19% of the anaphase I figures (as indicated by the gray portion of the bar graph). The remaining 21.4% appeared to be bridging that existed between homologous chromosomes (burgundy portion). Mutations in eflon suppressed overall anaphase I bridging in squashed preparations to 25.6% (n = 43, p<0.05, X2 test) and homologous chromosome bridging to 9.3% (p<0.1, X2 test). (C) Cap-H2Z3-0019/Cap-H2TH1 males have an elevated amount of meiosis I 4th-to-heterolog threads relative to wild-type and these are suppressible by teflon mutations. In prometaphase I to telophase I, 4th-to-heterolog threads occur in 19% of wild-type (n = 21), 42.5% in Cap-H2Z3-0019/Cap-H2TH1 (n = 40), and 6% in tefZ2-5549/tefZ2-5864; Cap-H2Z3-0019/Cap-H2TH1 (n = 50) squashed figures. The ability of teflon mutations to rescue Cap-H2 mutant 4th-to-heterolog threads was significant (p<0.00001, X2 test). (D) Bridged Cap-H2Z3-0019/Cap-H2TH1 anaphase I squashed figures. See also Figures 4 and 5. (A) Bridged tefZ2-5864/tefZ2-5549; Cap-H2Z3-0019/Cap-H2TH1 squashed anaphase I figures.
Mentions: The protein Teflon is implicated in the maintenance of Drosophila male meiosis I autosome conjunction as teflon mutants lose autosomal associations prior to anaphase I [31]. To investigate whether persistent associations between homologous chromosomes in anaphase I of Cap-H2 mutants (Figure 4B and 4C) are Teflon dependent, teflon mutations were crossed into a Cap-H2 mutant background and the frequency of anaphase I bridging was assessed. While 30.4% of anaphase I figures from Cap-H2Z3-0019/Cap-H2TH1 males were bridged (n = 102), bridging existed within only 10.8% of anaphase I figures from tefZ2-5549/tefZ2-5864; Cap-H2Z3-0019/Cap-H2TH1 males (n = 74, p<1×10−6, X2) (Figure 7A). Furthermore, in squashed preparations anaphase I bridging was decreased from 40.5% in Cap-H2Z3-0019/Cap-H2TH1 males (n = 42) to 25.6% in the tefZ2-5549/tefZ2-5864; Cap-H2Z3-0019/Cap-H2TH1 double mutants (n = 43, p<0.05, X2).

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