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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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A working model for the function of condensin II in the resolution of DNA entanglements between homologous and heterologous chromosomes prior to Drosophila male meiotic anaphase I.(A) In interphase nuclei, heterologous chromosomes intermingle and can naturally become entangled with one another because of their threadlike structure. Homologous chromosomes are also entangled as the pairing process likely leads to their raveling around one another. (B) In early prophase I, condensing II functions to promote territory formation. This either entails partial condensation of each bivalent into compact clusters of chromatin and/or the active sequestration of each bivalent into discrete chromosomal territories. In the course of condensing II mediated territory formation, DNA entanglements between heterologous chromosomes are resolved and/or their introduction is prevented (both depicted by large arrows). Paired homologs may also be individualized from one another during condensing II mediated chromosome organizational steps that occur during prophase I (depicted by small arrows). (B) Condensin II successfully promotes territory formation by late prophase I and heterologous chromosomes are individualized from one another. It is unclear whether condensin II functions after territory formation to further individualize homologs. In condensin II mutants, failure in the chromosome organizational steps during territory formation leads to entanglement persistence. (C) In wild-type metaphase I, little to no entanglements between chromosomes still exist. It is unclear, but feasible that condensin II mediated individualization is still present during metaphase I or at the transition into anaphase I. When condensin II is not functional, entanglements between homologous and heterologous chromosomes still exist. (D) In wild-type anaphase I, homologous chromosomes segregate from one another to daughter cells. When condensin II is mutant, persistent entanglements between heterologous and homologous chromosomes that were not resolved prior to anaphase I become revealed as chromatin bridges. Persistent entanglements may also lead to improper cosegregation of homologs or heterolog dragging to one pole (not shown). Note that our data cannot distinguish between the two following possible mechanisms: Condensin II resolves DNA entanglements prior to anaphase I and/or condensin II antagonizes another type of chromosomal association. In fact, mutations in teflon, a factor that promotes male autosomal conjunction, were capable of rescuing anaphase I bridging in Cap-H2 mutants. While this may be because Teflon protein induces and/or exacerbates DNA entanglements between heterologous and homologous chromosomes, it is plausible that Cap-H2 can antagonize a Teflon mediated homolog conjunction complex.
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pgen-1000228-g008: A working model for the function of condensin II in the resolution of DNA entanglements between homologous and heterologous chromosomes prior to Drosophila male meiotic anaphase I.(A) In interphase nuclei, heterologous chromosomes intermingle and can naturally become entangled with one another because of their threadlike structure. Homologous chromosomes are also entangled as the pairing process likely leads to their raveling around one another. (B) In early prophase I, condensing II functions to promote territory formation. This either entails partial condensation of each bivalent into compact clusters of chromatin and/or the active sequestration of each bivalent into discrete chromosomal territories. In the course of condensing II mediated territory formation, DNA entanglements between heterologous chromosomes are resolved and/or their introduction is prevented (both depicted by large arrows). Paired homologs may also be individualized from one another during condensing II mediated chromosome organizational steps that occur during prophase I (depicted by small arrows). (B) Condensin II successfully promotes territory formation by late prophase I and heterologous chromosomes are individualized from one another. It is unclear whether condensin II functions after territory formation to further individualize homologs. In condensin II mutants, failure in the chromosome organizational steps during territory formation leads to entanglement persistence. (C) In wild-type metaphase I, little to no entanglements between chromosomes still exist. It is unclear, but feasible that condensin II mediated individualization is still present during metaphase I or at the transition into anaphase I. When condensin II is not functional, entanglements between homologous and heterologous chromosomes still exist. (D) In wild-type anaphase I, homologous chromosomes segregate from one another to daughter cells. When condensin II is mutant, persistent entanglements between heterologous and homologous chromosomes that were not resolved prior to anaphase I become revealed as chromatin bridges. Persistent entanglements may also lead to improper cosegregation of homologs or heterolog dragging to one pole (not shown). Note that our data cannot distinguish between the two following possible mechanisms: Condensin II resolves DNA entanglements prior to anaphase I and/or condensin II antagonizes another type of chromosomal association. In fact, mutations in teflon, a factor that promotes male autosomal conjunction, were capable of rescuing anaphase I bridging in Cap-H2 mutants. While this may be because Teflon protein induces and/or exacerbates DNA entanglements between heterologous and homologous chromosomes, it is plausible that Cap-H2 can antagonize a Teflon mediated homolog conjunction complex.

Mentions: Figure 8 illustrates a working model of condensin II in Drosophila male meiosis to resolve both heterologous and homologous chromosomal associations. We speculate that these associations likely consist of DNA entanglements that naturally become introduced between interphase chromosomes due to their threadlike nature (Figure 8A). The studies herein identified a function for condensin II during prophase I, when paired homologous chromosomes become partitioned into discrete chromosomal territories [33]–[36]. We propose that condensin II either promotes this partitioning, by actively sequestering bivalents into different regions of the nucleus, or functions to perform prophase I chromosome condensation. It is important to stress that in both scenarios, the role of condensin II mediated territory formation is to ensure the individualization of heterologous chromosomes from one another (Figure 8B, large arrows). When sequestration into territories and/or condensation of the bivalents do not take place, i.e. in the condensin II mutants, individualization does not occur, heterologous entanglements persist into anaphase I, and chromosomes may become stretched to the point where variable sized chromosomal portions become lost (Figure 8E). Persistent heterologous entanglements may also lead to one chromosome dragging another to the incorrect pole (not shown).


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)

A working model for the function of condensin II in the resolution of DNA entanglements between homologous and heterologous chromosomes prior to Drosophila male meiotic anaphase I.(A) In interphase nuclei, heterologous chromosomes intermingle and can naturally become entangled with one another because of their threadlike structure. Homologous chromosomes are also entangled as the pairing process likely leads to their raveling around one another. (B) In early prophase I, condensing II functions to promote territory formation. This either entails partial condensation of each bivalent into compact clusters of chromatin and/or the active sequestration of each bivalent into discrete chromosomal territories. In the course of condensing II mediated territory formation, DNA entanglements between heterologous chromosomes are resolved and/or their introduction is prevented (both depicted by large arrows). Paired homologs may also be individualized from one another during condensing II mediated chromosome organizational steps that occur during prophase I (depicted by small arrows). (B) Condensin II successfully promotes territory formation by late prophase I and heterologous chromosomes are individualized from one another. It is unclear whether condensin II functions after territory formation to further individualize homologs. In condensin II mutants, failure in the chromosome organizational steps during territory formation leads to entanglement persistence. (C) In wild-type metaphase I, little to no entanglements between chromosomes still exist. It is unclear, but feasible that condensin II mediated individualization is still present during metaphase I or at the transition into anaphase I. When condensin II is not functional, entanglements between homologous and heterologous chromosomes still exist. (D) In wild-type anaphase I, homologous chromosomes segregate from one another to daughter cells. When condensin II is mutant, persistent entanglements between heterologous and homologous chromosomes that were not resolved prior to anaphase I become revealed as chromatin bridges. Persistent entanglements may also lead to improper cosegregation of homologs or heterolog dragging to one pole (not shown). Note that our data cannot distinguish between the two following possible mechanisms: Condensin II resolves DNA entanglements prior to anaphase I and/or condensin II antagonizes another type of chromosomal association. In fact, mutations in teflon, a factor that promotes male autosomal conjunction, were capable of rescuing anaphase I bridging in Cap-H2 mutants. While this may be because Teflon protein induces and/or exacerbates DNA entanglements between heterologous and homologous chromosomes, it is plausible that Cap-H2 can antagonize a Teflon mediated homolog conjunction complex.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1000228-g008: A working model for the function of condensin II in the resolution of DNA entanglements between homologous and heterologous chromosomes prior to Drosophila male meiotic anaphase I.(A) In interphase nuclei, heterologous chromosomes intermingle and can naturally become entangled with one another because of their threadlike structure. Homologous chromosomes are also entangled as the pairing process likely leads to their raveling around one another. (B) In early prophase I, condensing II functions to promote territory formation. This either entails partial condensation of each bivalent into compact clusters of chromatin and/or the active sequestration of each bivalent into discrete chromosomal territories. In the course of condensing II mediated territory formation, DNA entanglements between heterologous chromosomes are resolved and/or their introduction is prevented (both depicted by large arrows). Paired homologs may also be individualized from one another during condensing II mediated chromosome organizational steps that occur during prophase I (depicted by small arrows). (B) Condensin II successfully promotes territory formation by late prophase I and heterologous chromosomes are individualized from one another. It is unclear whether condensin II functions after territory formation to further individualize homologs. In condensin II mutants, failure in the chromosome organizational steps during territory formation leads to entanglement persistence. (C) In wild-type metaphase I, little to no entanglements between chromosomes still exist. It is unclear, but feasible that condensin II mediated individualization is still present during metaphase I or at the transition into anaphase I. When condensin II is not functional, entanglements between homologous and heterologous chromosomes still exist. (D) In wild-type anaphase I, homologous chromosomes segregate from one another to daughter cells. When condensin II is mutant, persistent entanglements between heterologous and homologous chromosomes that were not resolved prior to anaphase I become revealed as chromatin bridges. Persistent entanglements may also lead to improper cosegregation of homologs or heterolog dragging to one pole (not shown). Note that our data cannot distinguish between the two following possible mechanisms: Condensin II resolves DNA entanglements prior to anaphase I and/or condensin II antagonizes another type of chromosomal association. In fact, mutations in teflon, a factor that promotes male autosomal conjunction, were capable of rescuing anaphase I bridging in Cap-H2 mutants. While this may be because Teflon protein induces and/or exacerbates DNA entanglements between heterologous and homologous chromosomes, it is plausible that Cap-H2 can antagonize a Teflon mediated homolog conjunction complex.
Mentions: Figure 8 illustrates a working model of condensin II in Drosophila male meiosis to resolve both heterologous and homologous chromosomal associations. We speculate that these associations likely consist of DNA entanglements that naturally become introduced between interphase chromosomes due to their threadlike nature (Figure 8A). The studies herein identified a function for condensin II during prophase I, when paired homologous chromosomes become partitioned into discrete chromosomal territories [33]–[36]. We propose that condensin II either promotes this partitioning, by actively sequestering bivalents into different regions of the nucleus, or functions to perform prophase I chromosome condensation. It is important to stress that in both scenarios, the role of condensin II mediated territory formation is to ensure the individualization of heterologous chromosomes from one another (Figure 8B, large arrows). When sequestration into territories and/or condensation of the bivalents do not take place, i.e. in the condensin II mutants, individualization does not occur, heterologous entanglements persist into anaphase I, and chromosomes may become stretched to the point where variable sized chromosomal portions become lost (Figure 8E). Persistent heterologous entanglements may also lead to one chromosome dragging another to the incorrect pole (not shown).

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