High density of <scp>REC</scp>8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation

Agostinho, Ana; Manneberg, Otto; Schendel, Robin van; Hernández‐Hernández, Abrahan; Kouznetsova, Anna; Blom, Hans; Brismar, Hjalmar; Höög, Christer

doi:10.15252/embr.201642030

Cited by 41 publications

(61 citation statements)

References 57 publications

(135 reference statements)

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“…To explore the possibility that a Sororin-dependent cohesin stabilization event occurs during meiotic chromosome development, we investigated the localization of Sororin on chromosomes during meiotic prophase. Interestingly, Sororin shows a localization pattern distinct from that seen for meiotic cohesin, which was previously shown to colocalize with SYCP3 (Agostinho et al 2016). The results indicate that Sororin is enriched on chromosome cores at regions of synapsis between homologous chromosomes, with dynamics apparently related to formation of the tripartite SC complex, rather than the axial enrichment of cohesin.…”

Section: Discussionmentioning

confidence: 72%

Sororin is enriched at the central region of synapsed meiotic chromosomes

et al. 2017

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During meiotic prophase cohesin complexes mediate cohesion between sister chromatids and promote pairing and synapsis of homologous chromosomes. Precisely how the activity of cohesin is controlled to promote these events is not fully understood. In metazoans, cohesion establishment between sister chromatids during mitotic divisions is accompanied by recruitment of the cohesion-stabilizing protein Sororin. During somatic cell division cycles, Sororin is recruited in response to DNA replication-dependent modification of the cohesin complex by Esco acetyltransferases. How Sororin is recruited and acts in meiosis is less clear. Here we have surveyed the chromosomal localization of Sororin and its relationship to the meiotic cohesins and other chromatin modifiers with the objective of determining how Sororin contributes to meiotic chromosome dynamics. We show that Sororin localizes to the cores of meiotic chromosomes in a manner that is dependent on synapsis and the synaptonemal complex protein SYCP1. In contrast, cohesin, with which Sororin interacts in mitotic cells, shows axial enrichment on meiotic chromosomes even in the absence of synapsis between homologs. Using high-resolution microscopy, we show that Sororin is localized to the central region of the synaptonemal complex. These results indicate that Sororin regulation during meiosis is distinct from its regulation in mitotic cells, and may suggest that it interacts with a distinctly different partner to ensure proper chromosome dynamics in meiosis.

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Section: Discussionmentioning

confidence: 72%

Sororin is enriched at the central region of synapsed meiotic chromosomes

et al. 2017

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“…COs) along diplotene chromosomes, as illustrated for grasshopper and mouse (14,51,52). Moreover, a recent study using super-resolution microscopy in mouse meiocytes suggests that Rec8 prevents local separation of sister chromatid axes and illegitimate SC assembly (53,54). Studies of Sordaria prophase chromosomes further show that WT chromosomes exhibit axis splitting and loss of axis integrity specifically at CO sites and that this tendency is exaggerated when Rec8 is absent (14).…”

Section: Discussionmentioning

confidence: 99%

Meiotic prophase roles of Rec8 in crossover recombination and chromosome structure

et al. 2016

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Rec8 is a prominent component of the meiotic prophase chromosome axis that mediates sister chromatid cohesion, homologous recombination and chromosome synapsis. Here, we explore the prophase roles of Rec8. (i) During the meiotic divisions, Rec8 phosphorylation mediates its separase-mediated cleavage. We show here that such cleavage plays no detectable role for chromosomal events of prophase. (ii) We have analyzed in detail three rec8 phospho-mutants, with 6, 24 or 29 alanine substitutions. A distinct ‘separation of function’ phenotype is revealed. In the mutants, axis formation and recombination initiation are normal, as is non-crossover recombination; in contrast, crossover (CO)-related events are defective. Moreover, the severities of these defects increase coordinately with the number of substitution mutations, consistent with the possibility that global phosphorylation of Rec8 is important for these effects. (iii) We have analyzed the roles of three kinases that phosphorylate Rec8 during prophase. Timed inhibition of Dbf4-dependent Cdc7 kinase confers defects concordant with rec8 phospho-mutant phenotypes. Inhibition of Hrr25 or Cdc5/polo-like kinase does not. Our results suggest that Rec8's prophase function, independently of cohesin cleavage, contributes to CO-specific events in conjunction with the maintenance of homolog bias at the leptotene/zygotene transition of meiotic prophase.

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“…Accumulating evidence suggests that meiosis-specific cohesin complexes play essential roles not only in sister chromatid cohesion, but also in SC formation. However, it is largely elusive how distinct cohesin complexes exert their specific functions in sister chromatid cohesion and SC formation.Using super-resolution microscopic analyses (SIM and STED), Agostinho and colleagues have now examined chromosome axis and SC structures in mouse mutants defective in various cohesin subunits (Rec8, Stag3, or Smc1b) [6]. In wild-type spermatocytes, the chromosome axis, which consists of two sister chromatids, is labeled by a single line of the axial element (AE) component SYCP3.…”

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confidence: 99%

The cohesin REC8 prevents illegitimate inter‐sister synaptonemal complex assembly

Ishiguro

Watanabe

2016

EMBO Reports

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During meiosis, a specialized chromosome structure is assembled to promote pairing/ synapsis of homologous chromosomes and meiotic recombination, a process yielding chiasmata between homologs to ensure accurate segregation. Meiosis-specific cohesin complexes mediating sister chromatid cohesion play pivotal roles in almost all these events, including synaptonemal complex (SC) formation. In this issue of EMBO Reports, Agostinho and colleagues have examined chromosome axes and SC structures by taking advantage of a hypomorphic Stag3 mutant in which the levels of the cohesin subunit REC8 are partly reduced [6]. Using super-resolution microscopy, the authors illuminate previously unforeseen chromosome axis structures, showing locally separated axes in regions where REC8 is absent, regardless of RAD21L or RAD21 cohesin localization. Furthermore, they assessed the relationship between sister chromatid cohesion and inter-sister SC formation, demonstrating that "axial opening" in the REC8-free region is accompanied by illegitimate SC formation between sister chromatids. This study highlights the physiological importance of REC8 in sister chromatid cohesion and proper SC formation during meiosis, suggesting a new model in which a high density of REC8 deposition along the chromosome prevents illegitimate inter-sister SC formation. W hen chromosomes replicate in Sphase, sister chromatids are held together by a mechanism termed sister chromatid cohesion that enables accurate chromosome segregation in both mitosis and meiosis. In somatic cells, sister chromatid cohesion is mediated by the cohesin multi-protein complex, which is comprised of four core subunits: SMC1a and SMC3, the kleisin family protein RAD21, and either one of the accessory subunits SA1 and SA2. In mammalian germ cells, the cohesin complex contains in addition to RAD21 the meiosis-specific kleisin subunits REC8 and RAD21L [1][2][3] (Fig 1A). Furthermore, SMC1a and SA1/SA2 are largely replaced by other meiosis-specific cohesin subunits, SMC1b and STAG3, respectively [4,5]. Given that STAG3, SMC1b, and SMC3 are commonly shared in these meiotic cohesin complexes, it is assumed that the kleisin subunits REC8, RAD21L, and RAD21 have specific roles in the cohesin complexes during meiosis [1,2].In the meiotic prophase, REC8 is localized along chromosomes before meiotic DNA replication and persists throughout the first meiotic division and, at least at centromeres, until metaphase II. In contrast, RAD21L transiently appears on the chromosomes after DNA replication and culminates at the leptotene/ zygotene stage. While RAD21 is detectable in testicular mitotic cells, it is not detected in nuclei from early leptotene until zygotene, in contrast to the patterns of RAD21L and REC8. Thus, the kleisin subunits endow distinct cohesin complexes with different spatiotemporal localization patterns on chromosomes during meiotic prophase. Accumulating evidence suggests that meiosis-specific cohesin complexes play essential roles not only in sister chromatid cohesion, but also in...

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High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation

Cited by 41 publications

References 57 publications

Sororin is enriched at the central region of synapsed meiotic chromosomes

Sororin is enriched at the central region of synapsed meiotic chromosomes

Meiotic prophase roles of Rec8 in crossover recombination and chromosome structure

The cohesin REC8 prevents illegitimate inter‐sister synaptonemal complex assembly

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