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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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Chromosomes remain associated into anaphase I of Cap-H2 mutants.Metaphase I and anaphase I 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 3A indicates 10 µm and 5 µm in 3G). (A) Metaphase I in the wild-type. Each bivalent has congressed to the metaphase plate and appears as a cluster of DAPI stained material. (B) Anaphase I in the wild-type (DAPI only). Homologous chromosomes have segregated to daughter cells. (C) Anaphase I in the wild-type (DAPI and Tubulin merge). (D) Metaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male appears wild-type. (E) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male (DAPI only). Chromatin bridges can be seen in three different segregation events. (F) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male (DAPI and Tubulin merge). (G) Higher resolution wild-type anaphase I image showing complete segregation of homologs. (H) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant demonstrating extensive chromatin bridging due to persistent associations between chromosomes migrating to opposing poles. (I) Anaphase I bridge found from a Cap-D3EY00456 mutant.
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pgen-1000228-g003: Chromosomes remain associated into anaphase I of Cap-H2 mutants.Metaphase I and anaphase I 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 3A indicates 10 µm and 5 µm in 3G). (A) Metaphase I in the wild-type. Each bivalent has congressed to the metaphase plate and appears as a cluster of DAPI stained material. (B) Anaphase I in the wild-type (DAPI only). Homologous chromosomes have segregated to daughter cells. (C) Anaphase I in the wild-type (DAPI and Tubulin merge). (D) Metaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male appears wild-type. (E) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male (DAPI only). Chromatin bridges can be seen in three different segregation events. (F) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male (DAPI and Tubulin merge). (G) Higher resolution wild-type anaphase I image showing complete segregation of homologs. (H) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant demonstrating extensive chromatin bridging due to persistent associations between chromosomes migrating to opposing poles. (I) Anaphase I bridge found from a Cap-D3EY00456 mutant.

Mentions: During late prophase I of wild-type primary spermatocytes, chromosomes from each territory condense further and appear as three dots corresponding to the 2nd, 3rd and sex bivalents. This stage, referred to as M1 of meiosis I, may be morphologically abnormal in strong Cap-H2 mutants because it was not detected in our studies (n>50 testes). This is likely because these mutants fail to form normal chromosome territories. Proceeding further into meiosis, metaphase I is signified by the congression of the three bivalents into one cluster at the metaphase plate (Figure 3A). Despite not forming normal chromosome territories and possibly never reaching normal M1 chromosomal structure, there were no unusual features detected in Cap-H2 male sterile metaphase I figures (Figure 3D). Although subtle changes to chromosome morphology would not be detectable, it can be concluded that by metaphase I, gross chromosomal condensation occurs at least somewhat normally in Cap-H2 strong mutant males. This raises the interesting possibility that a gradual prophase I chromosome condensation is catalyzed by condensin II components in the course of chromosomal territory formation and culminates at M1. Next, a second condensation step to form metaphase I chromosomes occurs, which is only partially dependent or completely independent of condensin II components. Perhaps condensin I or some other factor is the major player for metaphase I chromosome assembly or compensates for condensin II loss.


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)

Chromosomes remain associated into anaphase I of Cap-H2 mutants.Metaphase I and anaphase I 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 3A indicates 10 µm and 5 µm in 3G). (A) Metaphase I in the wild-type. Each bivalent has congressed to the metaphase plate and appears as a cluster of DAPI stained material. (B) Anaphase I in the wild-type (DAPI only). Homologous chromosomes have segregated to daughter cells. (C) Anaphase I in the wild-type (DAPI and Tubulin merge). (D) Metaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male appears wild-type. (E) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male (DAPI only). Chromatin bridges can be seen in three different segregation events. (F) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male (DAPI and Tubulin merge). (G) Higher resolution wild-type anaphase I image showing complete segregation of homologs. (H) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant demonstrating extensive chromatin bridging due to persistent associations between chromosomes migrating to opposing poles. (I) Anaphase I bridge found from a Cap-D3EY00456 mutant.
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Related In: Results  -  Collection

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

pgen-1000228-g003: Chromosomes remain associated into anaphase I of Cap-H2 mutants.Metaphase I and anaphase I 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 3A indicates 10 µm and 5 µm in 3G). (A) Metaphase I in the wild-type. Each bivalent has congressed to the metaphase plate and appears as a cluster of DAPI stained material. (B) Anaphase I in the wild-type (DAPI only). Homologous chromosomes have segregated to daughter cells. (C) Anaphase I in the wild-type (DAPI and Tubulin merge). (D) Metaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male appears wild-type. (E) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male (DAPI only). Chromatin bridges can be seen in three different segregation events. (F) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant male (DAPI and Tubulin merge). (G) Higher resolution wild-type anaphase I image showing complete segregation of homologs. (H) Anaphase I from a Cap-H2Z3-0019/Cap-H2TH1 mutant demonstrating extensive chromatin bridging due to persistent associations between chromosomes migrating to opposing poles. (I) Anaphase I bridge found from a Cap-D3EY00456 mutant.
Mentions: During late prophase I of wild-type primary spermatocytes, chromosomes from each territory condense further and appear as three dots corresponding to the 2nd, 3rd and sex bivalents. This stage, referred to as M1 of meiosis I, may be morphologically abnormal in strong Cap-H2 mutants because it was not detected in our studies (n>50 testes). This is likely because these mutants fail to form normal chromosome territories. Proceeding further into meiosis, metaphase I is signified by the congression of the three bivalents into one cluster at the metaphase plate (Figure 3A). Despite not forming normal chromosome territories and possibly never reaching normal M1 chromosomal structure, there were no unusual features detected in Cap-H2 male sterile metaphase I figures (Figure 3D). Although subtle changes to chromosome morphology would not be detectable, it can be concluded that by metaphase I, gross chromosomal condensation occurs at least somewhat normally in Cap-H2 strong mutant males. This raises the interesting possibility that a gradual prophase I chromosome condensation is catalyzed by condensin II components in the course of chromosomal territory formation and culminates at M1. Next, a second condensation step to form metaphase I chromosomes occurs, which is only partially dependent or completely independent of condensin II components. Perhaps condensin I or some other factor is the major player for metaphase I chromosome assembly or compensates for condensin II loss.

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