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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 allelic combinations range from completely male sterile to only having detectable fertility loss when also heterozygous for an SMC4 mutation.(A) Seminal vesicle from Cap-H2 heterozygous male. The abundance of sperm is evident through the visualization of sperm heads (DAPI) and tails (don juan-GFP). Scale bar indicates 50 µm. (B) Seminal vesicle from a male sterile Cap-H2 mutant. DAPI and don juan-GFP illustrate the absence of mature sperm. (C) Cap-H2Z3-0019/Cap-H2Z3-5163 males had a fertility equivalent to Cap-H2Z3-5163/+ controls (p>0.05, two-tailed T-test assuming equal variances). Males were mated to wild-type females and the percent of eggs hatched was quantified. Data for each timepoint represent the same set of males with a different brood of females. (D) The introduction of a mutant SMC4 allele into the Cap-H2Z3-0019/Cap-H2Z3-5163 mutant background reduced fertility compared to SMC4; Cap-H2 double heterozygous controls (p<0.05, two-tailed T-test assuming equal variances). No other pairwise comparison was found to be significant (p>0.05).
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pgen-1000228-g001: Cap-H2 allelic combinations range from completely male sterile to only having detectable fertility loss when also heterozygous for an SMC4 mutation.(A) Seminal vesicle from Cap-H2 heterozygous male. The abundance of sperm is evident through the visualization of sperm heads (DAPI) and tails (don juan-GFP). Scale bar indicates 50 µm. (B) Seminal vesicle from a male sterile Cap-H2 mutant. DAPI and don juan-GFP illustrate the absence of mature sperm. (C) Cap-H2Z3-0019/Cap-H2Z3-5163 males had a fertility equivalent to Cap-H2Z3-5163/+ controls (p>0.05, two-tailed T-test assuming equal variances). Males were mated to wild-type females and the percent of eggs hatched was quantified. Data for each timepoint represent the same set of males with a different brood of females. (D) The introduction of a mutant SMC4 allele into the Cap-H2Z3-0019/Cap-H2Z3-5163 mutant background reduced fertility compared to SMC4; Cap-H2 double heterozygous controls (p<0.05, two-tailed T-test assuming equal variances). No other pairwise comparison was found to be significant (p>0.05).

Mentions: To determine whether the primary defect leading to loss of fertility in Cap-H2 mutant males is pre or post copulation, Cap-H2Z3-0019 homozygous mutant and heterozygous control siblings were engineered to carry a sperm tail marker, don juan-GFP, and aged in the absence of females to allow sperm to accumulate in the seminal vesicles. In contrast to Cap-H2Z3-0019 heterozygous control males where the seminal vesicles fill with sperm, those from Cap-H2Z3-0019 homozygous males were seemingly devoid of sperm as no DAPI staining sperm heads or don juan-GFP positive sperm tails were detectable (Figure 1A and 1B). The lack of mature sperm in the seminal vesicles confirmed that sterility in Cap-H2 mutant males is attributed to a defect in gamete production.


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 allelic combinations range from completely male sterile to only having detectable fertility loss when also heterozygous for an SMC4 mutation.(A) Seminal vesicle from Cap-H2 heterozygous male. The abundance of sperm is evident through the visualization of sperm heads (DAPI) and tails (don juan-GFP). Scale bar indicates 50 µm. (B) Seminal vesicle from a male sterile Cap-H2 mutant. DAPI and don juan-GFP illustrate the absence of mature sperm. (C) Cap-H2Z3-0019/Cap-H2Z3-5163 males had a fertility equivalent to Cap-H2Z3-5163/+ controls (p>0.05, two-tailed T-test assuming equal variances). Males were mated to wild-type females and the percent of eggs hatched was quantified. Data for each timepoint represent the same set of males with a different brood of females. (D) The introduction of a mutant SMC4 allele into the Cap-H2Z3-0019/Cap-H2Z3-5163 mutant background reduced fertility compared to SMC4; Cap-H2 double heterozygous controls (p<0.05, two-tailed T-test assuming equal variances). No other pairwise comparison was found to be significant (p>0.05).
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Related In: Results  -  Collection

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

pgen-1000228-g001: Cap-H2 allelic combinations range from completely male sterile to only having detectable fertility loss when also heterozygous for an SMC4 mutation.(A) Seminal vesicle from Cap-H2 heterozygous male. The abundance of sperm is evident through the visualization of sperm heads (DAPI) and tails (don juan-GFP). Scale bar indicates 50 µm. (B) Seminal vesicle from a male sterile Cap-H2 mutant. DAPI and don juan-GFP illustrate the absence of mature sperm. (C) Cap-H2Z3-0019/Cap-H2Z3-5163 males had a fertility equivalent to Cap-H2Z3-5163/+ controls (p>0.05, two-tailed T-test assuming equal variances). Males were mated to wild-type females and the percent of eggs hatched was quantified. Data for each timepoint represent the same set of males with a different brood of females. (D) The introduction of a mutant SMC4 allele into the Cap-H2Z3-0019/Cap-H2Z3-5163 mutant background reduced fertility compared to SMC4; Cap-H2 double heterozygous controls (p<0.05, two-tailed T-test assuming equal variances). No other pairwise comparison was found to be significant (p>0.05).
Mentions: To determine whether the primary defect leading to loss of fertility in Cap-H2 mutant males is pre or post copulation, Cap-H2Z3-0019 homozygous mutant and heterozygous control siblings were engineered to carry a sperm tail marker, don juan-GFP, and aged in the absence of females to allow sperm to accumulate in the seminal vesicles. In contrast to Cap-H2Z3-0019 heterozygous control males where the seminal vesicles fill with sperm, those from Cap-H2Z3-0019 homozygous males were seemingly devoid of sperm as no DAPI staining sperm heads or don juan-GFP positive sperm tails were detectable (Figure 1A and 1B). The lack of mature sperm in the seminal vesicles confirmed that sterility in Cap-H2 mutant males is attributed to a defect in gamete production.

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