The cohesion protein ORD is required for homologue bias during meiotic recombination

Abstract

During meiosis, sister chromatid cohesion is required for normal levels of homologous recombination, although how cohesion regulates exchange is not understood. Null mutations in orientation disruptor (ord) ablate arm and centromeric cohesion during Drosophila meiosis and severely reduce homologous crossovers in mutant oocytes. We show that ORD protein localizes along oocyte chromosomes during the stages in which recombination occurs. Although synaptonemal complex (SC) components initially associate with synapsed homologues in ord mutants, their localization is severely disrupted during pachytene progression, and normal tripartite SC is not visible by electron microscopy. In ord germaria, meiotic double strand breaks appear and disappear with frequency and timing indistinguishable from wild type. However, Ring chromosome recovery is dramatically reduced in ord oocytes compared with wild type, which is consistent with the model that defects in meiotic cohesion remove the constraints that normally limit recombination between sisters. We conclude that ORD activity suppresses sister chromatid exchange and stimulates inter-homologue crossovers, thereby promoting homologue bias during meiotic recombination in Drosophila.

Functional links between Drosophila Nipped-B and cohesin in somatic and meiotic cells

“…In contrast to Nipped-B, bright staining for the cohesion proteins Ord and Smc1/Smc3 is visible in centromeric heterochromatin, which is identified by bright diamidinophenylindole staining and immunostaining for the CID centromere-specific histone ( Fig. 6; Khetani and Bickel 2007;Webber et al 2004). These data suggest that Nipped-B may not associate strongly with meiotic centromeres and are consistent with the lack of Nipped-B signal at the centromeres of polytene chromosomes.…”

“…6). It also colocalizes with the Ord protein, which is required for meiotic cohesion in both sexes and SC maintenance in oocytes (Bickel et al 1997;Khetani and Bickel 2007;Webber et al 2004), and with C(3)G, a transverse filament protein that resides within the central element of the SC (Anderson et al 2005). These data argue that Nipped-B may play a direct role in regulating meiotic cohesion as well as SC structure and function.…”

“…Intact ovaries whole-mount preparations were fixed and stained as described previously (Webber et al 2004). Z-stacks were collected and deconvolved using the Improvision Volocity software.…”

Evolutionary history of the mammalian synaptonemal complex

“…The central element components stabilize the head-to-head interaction of the opposing transverse filaments in the middle of the SC. The diagram is adapted from Schramm 2011. Webber et al 2004Gause et al 2010;Lake and Hawley 2012).…”

“…HTP-3, therefore, seems to function as a key regulator for the assembly of the AEs recruiting cohesin and non-cohesin proteins to the chromosome axes. In Drosophila, the ORD protein is essential for wild-type SC morphology but also for the stable association of cohesins with the chromosomes (Page and Hawley 2004;Webber et al 2004).…”