Sororin loads to the synaptonemal complex central region independently of meiotic cohesin complexes

Gómez, Rocío; Felipe‐Medina, Natalia; Ruiz‐Torres, Miguel; Berenguer, Inés; Viera, Alberto; Pérez, Sara; Barbero, José Luís; Llano, Elena; Fukuda, Tomoyuki; Alsheimer, Manfred; Pendás, Alberto M.; Losada, Ana; Suja, José Á.

doi:10.15252/embr.201541060

Cited by 28 publications

(36 citation statements)

References 66 publications

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“…The timing with which Sororin loads on meiotic chromosomes and its patterns of localization are different from what has been observed in mitotic cells and suggest Sororin may have roles in synapsis that are distinct from its role in regulating mitotic cohesin. Our results are consistent with and extend upon recent studies showing that Sororin is expressed in meiotic cells and localizes to synapsed meiotic chromosomes (Gómez et al 2016). …”

Section: Introductionsupporting

confidence: 93%

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: Introductionsupporting

confidence: 93%

Sororin is enriched at the central region of synapsed meiotic chromosomes

et al. 2017

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“…11). Similarly, the regulatory cohesin subunit Sororin, which is located at the CE27, is also lacking in Six6os1 -deficient spermatocytes (Supplementary Fig. 8).…”

Section: Resultsmentioning

confidence: 89%

“…We co-transfected Six6os1 with cDNAs encoding each of the known central element proteins (SYCE1, SYCE2, SYCE3 and TEX12), transverse filament protein SYCP1, LE protein SYCP3, and the meiotic cohesins REC8 and Sororin (a recently identified cohesin subunit localized to synapsed regions27) (Fig. 3a; Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility

et al. 2016

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Meiotic recombination generates crossovers between homologous chromosomes that are essential for genome haploidization. The synaptonemal complex is a ‘zipper'-like protein assembly that synapses homologue pairs together and provides the structural framework for processing recombination sites into crossovers. Humans show individual differences in the number of crossovers generated across the genome. Recently, an anonymous gene variant in C14ORF39/SIX6OS1 was identified that influences the recombination rate in humans. Here we show that C14ORF39/SIX6OS1 encodes a component of the central element of the synaptonemal complex. Yeast two-hybrid analysis reveals that SIX6OS1 interacts with the well-established protein synaptonemal complex central element 1 (SYCE1). Mice lacking SIX6OS1 are defective in chromosome synapsis at meiotic prophase I, which provokes an arrest at the pachytene-like stage and results in infertility. In accordance with its role as a modifier of the human recombination rate, SIX6OS1 is essential for the appropriate processing of intermediate recombination nodules before crossover formation.

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“…PDS5B is present in spermatogonia and spermatocytes and during meiotic prophase is associated with the AE independently of the presence of synaptonemal complex proteins (Fukuda and Hoog, 2010). Sororin is also localized within the central element of the SC independently of the presence of cohesin (Gomez et al, 2016). However, to date, the function of these proteins, and the importance of the prophase pathway in mammalian meiosis remain undescribed.…”

Section: Introductionmentioning

confidence: 99%

Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse

et al. 2016

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Summary Mammalian NIMA-like kinase-1 (NEK1) is a dual-specificity kinase highly expressed in mouse germ cells during prophase I of meiosis. Loss of NEK1 induces retention of cohesin on chromosomes at meiotic prophase I. Timely deposition and removal of cohesin is essential for accurate chromosome segregation. Two processes regulate cohesin removal: a non-proteolytic mechanism involving WAPL, Sororin, and PDS5B and direct cleavage by Separase. Herein, we demonstrate a role for NEK1 in the regulation of WAPL loading during meiotic prophase I, via an interaction between NEK1 and PDS5B. This regulation of WAPL by NEK1-PDS5B is mediated by the protein phosphatase PP1γ, which both interacts with, and is a phosphotarget, of NEK1. Taken together, our results reveal that NEK1 phosphorylates PP1γ leading to dephosphorylation of WAPL, which in turn results in its retention on chromosome cores to promote loss of cohesion at the end of prophase I in mammals.

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Sororin loads to the synaptonemal complex central region independently of meiotic cohesin complexes

Cited by 28 publications

References 66 publications

Sororin is enriched at the central region of synapsed meiotic chromosomes

Sororin is enriched at the central region of synapsed meiotic chromosomes

C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility

Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse

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