SYCP2 and SYCP3 are required for cohesin core integrity at diplotene but not for centromere cohesion at the first meiotic division

Abstract

Much of the organization of the meiotic prophase-I chromosome axis is attributed to two groups of proteins: the axial element proteins, SYCP2 and SYCP3; and the cohesin-complex proteins. Although the cohesin-complex proteins ensure that sister chromatids remain paired during meiosis, the role of SYCP2 and SYCP3 is not clear. Interestingly, it has been shown that SYCP3 and SYCP2 associate with the centromere regions of male, but not female, metaphase-I chromosomes, suggesting a sex-specific function for the two proteins. We have analysed the spatial distribution of cohesin-complex proteins associated with meiotic chromosomes in germ cells derived from Sycp3-deficient female and male mice. We show that, in the absence of SYCP3, the cohesin cores associated with the female meiotic chromosomes disassemble prematurely at the diplotene stage of meiosis. We also show that SYCP3 and SYCP2 are not required for centromere cohesion at the metaphase-I stage in male germ cells. We conclude that SYCP3 has a temporally restricted role in maintaining, but not establishing, cohesin-core organization during prophase I. This finding supports a model in which the removal of bulk cohesin from paired sister chromatids at late prophase in both meiotic and mitotic cells ensures proper chromosome compaction and segregation.

Genetic Evidence That Synaptonemal Complex Axial Elements Govern Recombination Pathway Choice in Mice

“…Alternatively, our results may be consistent with the Kim et al (2010) finding that in later stages of recombination, yeast Rec8 acts to enforce IH bias. Kouznetsova et al (2005) observed that the lateral axis SC structure in Sycp3 2/2 oocytes has discontinuities in staining for cohesins including STAG3 and REC8. These local disruptions of the cohesin complex may compromise IH bias.…”

“…Sycp3 2/2 may reflect a general role for the SC in partner choice/BSCR function. Supportive of this possibility is that although axial elements form on pachytene chromosomes of SYCP3-deficient oocytes, they are abnormal and have discontinuities in the axis structure (Kouznetsova et al 2005). If the axial element itself is governing partner choice, this would predict that deletion of other axial element components would have similar effects.…”

DNA double strand break repair, chromosome synapsis and transcriptional silencing in meiosis

“…RPA is then replaced by RAD51, with the aid of mediators such as also important for correct homologous chromosome pairing and crossover formation. [12][13][14] For example, in male Sycp3 knockout mice, many chromosomes remain asynapsed or show heterologous synapsis, and the spermatocytes become apoptotic around the developmental phase that corresponds to midpachytene in wild type, the stage at which all autosomal chromosomes should have achieved complete synapsis. 12 Many mutants that have pairing and DSB repair abnormalities, show asynapsis at pachytene, resulting in apoptosis around this stage.…”

“…In general, ATM appears to be rapidly recruited to DSB sites, followed by later accumulation of ATR. Conversely, large 13 1 bivalent. The small translocation bivalent shows complete synapsis in only 40% of the nuclei, whereas the larger bivalent is completely synapsed in more then 95% of the nuclei.…”

“…For example, in mice carrying two similar but not identical translocations between chromosome 1 and chromosome 13, a heterologous region of approximately 40 Mb is present on both the small 1 13 bivalent and the DSB repair pathway. This could explain why γH2AX is not formed on XY chromatin in Brca1 mutant mouse spermatocytes.…”