Condensin II Resolves Chromosomal Associations to Enable Anaphase I Segregation in Drosophila Male Meiosis

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.

Drosophila rae1 is required for male meiosis and spermatogenesis

“…The analysis of GFP-tagged RAE1 distribution in wildtype meiosis I cells indicated co-localization of RAE1 with chromatin starting from late prophase primary spermatocytes until ana/telophase I nuclei, thus suggesting that the role of RAE1 in chromatin condensation may be more direct. In meiosis, bivalents need to reach a correct condensation state during late G2/prophase I to ensure a faithful chromosome partitioning to daughter cells, through the resolution of homologous associations, necessary to prevent chromatin bridges (Hartl et al, 2008). Hence, defective chromosome condensation could explain the lagging chromosomes and anaphase bridges, culminating in an uneven chromosome segregation to the opposite cell poles of the first meiotic division.…”

Condensins: universal organizers of chromosomes with diverse functions

“…It remains to be determined whether the fivesubunit condensin II complex is present in Drosophila because the gene encoding CAP-G2 has not yet been found in the sequenced region of the Drosophila genome. Currently available evidence suggests that the putative condensin II subunits (CAP-D3 and CAP-H2) may not play a major role in mitotic chromosome organization and segregation (Savvidou et al 2005;Oliveira et al 2007) and that they have meiotic functions instead, making a crucial contribution to anaphase I chromosome segregation (Hartl et al 2008b;see below).…”

“…Although mitotic cells express them, it appears that they do not play major functions in mitotic chromosome assembly or segregation (Savvidou et al 2005). Instead, a recent genetic study has shown that both CAP-D3 and CAP-H2 are necessary for male fertility (Hartl et al 2008b). Cap-H2 mutants display defects in chromosome territory formation in prophase I, which in turn result in a failure to resolve heterologous and/or homologous chromosomes in anaphase I.…”

Structural maintenance of chromosome complexes and bone development: the beginning of a wonderful relationship?

“…Condensin is involved in the expression regulation of the recombinant DNA and transfer RNA genes in budding and fission yeast and in the organization of polytene chromosomes in Drosophila. [22][23][24] Condensin is involved in T-and B-cell development and maintenance of quiescence state by regulating the accessibility of transcription factors to chromatin. 25,26 Many of our knowledge of the roles of condensin in the regulation of interphase chromosome come from studies of the dosage compensation complex (DCC) present in Caenorhabditis elegans.…”