Affinage

REC8

Meiotic recombination protein REC8 homolog · UniProt O95072

Length
547 aa
Mass
62.6 kDa
Annotated
2026-04-28
85 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

REC8 is a meiosis-specific α-kleisin subunit of the cohesin complex that establishes and maintains sister chromatid cohesion during meiotic divisions, organizes chromosome axes, restricts synaptonemal complex formation to homologs, and guides the distribution of meiotic double-strand breaks. REC8 forms a ring complex with SMC1β, SMC3, and STAG3, loads onto chromosomes during pre-meiotic S phase, and persists on chromosome arms until anaphase I and at centromeres until anaphase II; stepwise removal is controlled by phosphorylation-dependent separase cleavage, with CK1δ/ε, DDK, and Aurora B/C kinases phosphorylating Rec8 to promote arm cleavage at meiosis I, while shugoshin-PP2A dephosphorylates centromeric Rec8 to protect it, and meikin-polo kinase phosphorylation additionally regulates both centromeric cohesion protection and monopolar kinetochore orientation (PMID:10440376, PMID:12759374, PMID:14532136, PMID:20230747, PMID:20383139, PMID:35385691, PMID:33888556, PMID:38448160). Rec8 cohesin established during fetal DNA replication is maintained without turnover throughout oocyte arrest, and its cleavage at meiosis I is both necessary and sufficient to convert sister kinetochores from co-orientation to bi-orientation (PMID:20971813, PMID:26898469, PMID:34758289). The separase-generated C-terminal Rec8 fragment is degraded by the Ate1-dependent N-end rule pathway, and failure of this degradation causes spermatocyte apoptosis (PMID:26858254).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1999 High

    Identification of Rec8 as a meiosis-specific cohesin subunit established the molecular basis for differential cohesion at centromeres versus arms during the two meiotic divisions, resolving how reductional segregation is achieved.

    Evidence Genetic deletion in fission yeast with immunolocalization and segregation analysis; parallel expression and phosphorylation analysis

    PMID:10207075 PMID:10440376

    Open questions at the time
    • Separase involvement not yet demonstrated
    • Mammalian Rec8 function unconfirmed
    • Mechanism of centromeric versus arm differential removal unknown
  2. 2003 High

    Demonstration that mammalian REC8 associates with SMC1β/SMC3 and axial element components, and that separase cleavage of Rec8 is required for meiotic chromosome segregation, defined the core cohesin ring composition and cleavage-dependent removal mechanism.

    Evidence Co-immunoprecipitation of REC8 with SMC1β/SMC3/SCP3/RAD51 in rat and mouse spermatocytes; non-cleavable Rec8 mutant in fission yeast blocking meiosis I

    PMID:12615909 PMID:12759374 PMID:14532136

    Open questions at the time
    • Kinases responsible for phosphorylation-dependent cleavage not identified
    • Centromeric protection mechanism unknown
    • Non-cleavable mutant not yet tested in mammals
  3. 2005 High

    Knockout of REC8 in mice revealed that REC8 restricts synaptonemal complex formation to homologs rather than sister chromatids, establishing a structural gatekeeping role beyond simple cohesion.

    Evidence Rec8 knockout mouse with cytological analysis showing inter-sister rather than inter-homolog synapsis

    PMID:15935783

    Open questions at the time
    • Mechanism by which REC8 prevents sister-chromatid synapsis unclear
    • Relationship between REC8 density on axes and synapsis restriction not quantified
  4. 2006 High

    Discovery that Rec8 phosphorylation enables stepwise arm-then-centromere cohesion loss, opposed by shugoshin at centromeres, resolved the long-standing question of how differential cohesion removal is regulated between meiosis I and II.

    Evidence Phosphorylation-site mutagenesis and sgo1 epistasis in budding yeast; anti-Rec8 antibody microinjection at defined meiotic stages in mouse oocytes

    PMID:16672979 PMID:16855401

    Open questions at the time
    • Identity of the kinase(s) phosphorylating Rec8 not yet established
    • Precise phosphorylation sites not mapped
  5. 2009 High

    In vitro cleavage assays and non-cleavable Rec8 transgenic mice confirmed that separase cleavage of phosphorylated Rec8 is essential for mammalian meiosis I, while genome-wide ChIP showed Rec8 guides Spo11-mediated DSB distribution along chromosomes.

    Evidence In vitro separase cleavage of phosphorylated Rec8; Rec8-N non-cleavable transgenic mouse; genome-wide ChIP-chip in yeast with rec8 deletion

    PMID:19439448 PMID:19625504

    Open questions at the time
    • Specific kinases for mammalian Rec8 phosphorylation not identified
    • Mechanism linking Rec8 binding to Spo11 recruitment unclear
  6. 2010 High

    Identification of CK1δ/ε and DDK as the kinases phosphorylating Rec8, with PP2A-shugoshin opposing them at centromeres, completed the kinase-phosphatase circuit governing stepwise cohesion removal; separately, TEV-cleavable Rec8 knockin mice proved that Rec8-containing cohesin established during fetal S phase is maintained without turnover throughout oocyte arrest.

    Evidence Kinase inhibition and phosphomimetic Rec8 mutants in budding and fission yeast; mass spectrometry phosphorylation mapping; TEV-cleavable Rec8 knockin with live imaging in mouse oocytes

    PMID:20230747 PMID:20383139 PMID:20581463 PMID:20971813

    Open questions at the time
    • Whether the same kinases operate in mammalian meiosis not yet shown
    • Turnover absence demonstrated only for months; lifetime persistence not directly tested
    • DDK versus CK1 relative contributions at specific sites unclear
  7. 2014 High

    STAG3 was shown to stabilize REC8-containing cohesin complexes and to be specifically required for meiotic chromosome axis compaction and synapsis, establishing STAG3 as the obligate SA subunit for meiotic REC8 cohesin function.

    Evidence Stag3 hypomorphic knockin mouse with reduced REC8 cohesin levels and axis/synapsis defects

    PMID:24797475

    Open questions at the time
    • Whether STAG3 is required for REC8 loading in vivo or only for stability not fully resolved
    • Structural basis of STAG3-REC8 specificity unknown
  8. 2016 High

    Multiple advances clarified REC8 cohesin maintenance and clearance: confirmation that no cohesion renewal occurs in arrested oocytes, discovery that the Rec8 C-terminal cleavage fragment is destroyed via Ate1-mediated N-end rule degradation (required for male fertility), super-resolution mapping showing high REC8 density prevents illegitimate inter-sister synapsis, and phospho-mutant series separating DDK-dependent Rec8 phosphorylation roles in crossover control from axis formation.

    Evidence Inducible Rec8 activation in arrested oocytes; Ate1 conditional KO mouse with Rec8 fragment accumulation; STED microscopy in Stag3 hypomorph; systematic Rec8 phospho-alanine substitution series with timed DDK inhibition

    PMID:26858254 PMID:26898469 PMID:27170622 PMID:27484478

    Open questions at the time
    • N-end rule pathway for Rec8 fragment shown only in spermatogenesis; oocyte relevance untested
    • DDK phosphorylation sites promoting crossovers versus separase cleavage not fully distinguished
    • Inter-sister synapsis suppression mechanism beyond physical density not characterized
  9. 2018 High

    Ectopic expression studies demonstrated that Rec8-STAG3 cohesin is regulated by the canonical Wapl/sororin cohesion maintenance pathway, and that Rec8 physically interacts with the LINC complex component Mps3 to control nuclear envelope dynamics during meiosis.

    Evidence Rec8-STAG3 co-expression in HEK293 cells with Wapl/sororin knockdown; Rec8-Mps3 co-IP and ectopic expression in mitotic yeast

    PMID:29724914 PMID:30417519

    Open questions at the time
    • Wapl/sororin regulation of Rec8 cohesin not validated in native meiotic cells
    • Mps3 interaction shown only by co-IP in single lab
    • Functional consequence of Mps3-Rec8 interaction on chromosome movement unclear
  10. 2021 High

    REC8 cleavage by separase at meiosis I was shown to be necessary and sufficient to convert sister kinetochores from co-orientation to bi-orientation, and meikin-polo kinase was found to phosphorylate Rec8 to potentiate PP2A-shugoshin centromeric protection, establishing dual functions of Rec8 phosphorylation in orientation and protection.

    Evidence Spindle-chromosome complex transfer between meiosis I and II oocytes with selective REC8 cleavage; Moa1-Plo1 kinase assays with Rec8 phosphosite dissection and sgo1-PP2A epistasis in fission yeast

    PMID:33888556 PMID:34758289

    Open questions at the time
    • Mammalian meikin-Rec8 phosphorylation sites not mapped
    • How pericentromeric Rec8 cleavage mechanistically triggers bi-orientation switch unknown
  11. 2022 High

    Aurora B/C kinase was identified as an additional kinase phosphorylating Rec8 to promote separase cleavage in mammalian oocytes, extending the multi-kinase circuit; separately, a non-meiotic role for REC8 in stabilizing MAVS and STING during antiviral innate immune signaling was reported.

    Evidence Rec8-cleavage biosensor in mouse oocytes with Aurora B/C inhibition and phosphomutant analysis; co-IP of REC8 with MAVS/STING, ubiquitination assays, and REC8 knockdown during viral infection

    PMID:35107381 PMID:35385691

    Open questions at the time
    • Relative contributions of Aurora B/C versus CK1/DDK in mammalian Rec8 phosphorylation not quantified
    • Non-meiotic REC8 function in innate immunity reported by single lab and awaits independent confirmation
    • Whether REC8's immune role is physiologically relevant given its meiotic-specific expression pattern is unclear
  12. 2024 High

    Phosphorylation of Rec8 (and Psm3) at specific polo-kinase sites was genetically separated from cohesion protection and shown to be specifically required for monopolar kinetochore orientation, and acetylation of Rec8 cohesin at Psm3-K1013 by Eso1 was found necessary for reductional segregation, revealing post-translational modification of the Rec8 complex beyond phosphorylation.

    Evidence Non-phosphorylatable Rec8/Psm3 mutants with kinetochore orientation assay; mass spectrometry identification of Psm3 acetylation in purified meiotic centromeric Rec8 complexes with acetylation-site mutants

    PMID:38448160 PMID:38575358

    Open questions at the time
    • Whether Psm3 acetylation functions are conserved in mammals unknown
    • Structural basis for how Rec8 phosphorylation enables monopolar attachment not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the Rec8 cohesin ring at atomic resolution, how REC8 density mechanistically prevents inter-sister synapsis, the full integration of multiple kinase inputs (CK1, DDK, Aurora B/C, Plo1) on Rec8 in a single mammalian model, and whether the reported non-meiotic immune function of REC8 is physiologically relevant.
  • No atomic-resolution structure of Rec8-containing cohesin
  • Mechanism linking Rec8 to inter-sister synapsis prevention not established beyond density model
  • Integrated kinase circuit for Rec8 phosphorylation not validated in a single mammalian system

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005694 chromosome 10 GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 10 R-HSA-1474165 Reproduction 6 R-HSA-73894 DNA Repair 3
Partners
ESPL1EWSR1PDS5SGO1SMC1BSMC3STAG3WAPL
Complex memberships
Meiotic cohesin (REC8-SMC1β-SMC3-STAG3)Synaptonemal complex (axial element association)

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Fission yeast Rec8 is a meiosis-specific cohesin subunit that localizes to centromeres and chromosome arms during pre-meiotic S phase. Centromeric Rec8 persists throughout meiosis I and is lost at anaphase II. Deletion of rec8 causes precocious sister chromatid separation at meiosis I, resulting in equational rather than reductional chromosome segregation, demonstrating that Rec8 is required for centromeric cohesion and for orienting sister kinetochores to the same pole during meiosis I. Genetic deletion (rec8 knockout), immunolocalization, chromosome segregation analysis in fission yeast Nature High 10440376
1999 Rec8p is phosphorylated prior to meiosis I (as shown by analysis of the mei4 mutant blocked before meiosis I) and is expressed only during meiosis. Rec8p localizes to approximately 100 foci per prophase nucleus. A human ortholog (hREC8) exists with significant sequence similarity and germ-cell-specific expression. Protein expression analysis by Western blot, immunolocalization, mei4/mes1 mutant analysis, meiosis-specific induction Molecular and cellular biology High 10207075
2003 Mammalian REC8 protein associates with meiotic cohesin subunits SMC1beta and SMC3 (but not SMC1alpha) and with synaptonemal complex component SCP3, as shown by immunoprecipitation. REC8 localizes along axial/lateral elements during prophase I and persists on chromosome arms until anaphase I and at centromeres until anaphase II, providing arm cohesion at metaphase I and centromeric cohesion until anaphase II. Immunoprecipitation (co-IP), immunohistochemistry, Western blot (phosphorylation state), chromosome spread immunofluorescence Journal of cell science High 12759374
2003 Meiotic cohesin REC8 marks axial elements before SMC1beta, SMC3, SCP2, and SCP3, appearing from pre-meiotic S phase and providing a structural basis for axial element (AE) formation. RAD51 and/or DMC1 co-immunoprecipitates with REC8, suggesting REC8 may scaffold recombination complexes on the AE. Immunofluorescence, co-immunoprecipitation, chromosome spread analysis in rat spermatocytes The Journal of cell biology High 12615909
2003 Separase cleavage of Rec8 is required for meiotic chromosome segregation in fission yeast. A non-cleavable form of Rec8 blocks homolog disjunction at meiosis I. Rec8 forms distinct arm complexes with Rec11 (SA3) and centromeric complexes with Psc3 (SA1/SA2), and cleavage of arm Rec8 is required for meiosis I while centromeric Rec8 cleavage is required for meiosis II. Non-cleavable Rec8 mutant expression, genetic epistasis with rec11 deletion, chromosome segregation analysis The EMBO journal High 14532136
2005 Mouse REC8 null mutants of both sexes are sterile with germ cell failure. In the absence of REC8, early chromosome pairing is normal but synapsis occurs between sister chromatids rather than homologous chromosomes, demonstrating that a major role of REC8 in mammalian meiosis is to restrict synaptonemal complex formation to homologs. Rec8 knockout mouse, cytological analysis of meiotic chromosomes, immunofluorescence Developmental cell High 15935783
2006 Phosphorylation of the cohesin subunit Rec8 contributes to step-wise cohesin removal during meiosis. Loss of arm cohesion at meiosis I requires Rec8 phosphorylation, and the cohesin protector Sgo1 prevents premature loss of centromeric cohesion by opposing this phosphorylation. Meiotic recombination also contributes to step-wise cohesin loss. Phosphorylation site mutagenesis, epistasis analysis with sgo1 and recombination mutants in budding yeast, cohesin localization assays Nature High 16672979
2006 Loss of arm REC8 (but not centromeric REC8) is required for homolog separation at meiosis I in mouse oocytes, while loss of centromeric REC8 is required for sister chromatid separation at meiosis II. Neither loss is required for cytokinesis/polar body emission. This was demonstrated by microinjection of anti-Rec8 antibody at different meiotic stages, and securin destruction (via the spindle checkpoint-proteasome pathway) was shown to regulate arm REC8 removal. Antibody microinjection into mouse oocytes, inhibitor treatments (proteasome inhibitor, topoisomerase II inhibitor, PP2A inhibitor), chromosome segregation analysis Cell cycle (Georgetown, Tex.) High 16855401
2009 Separase cleaves mouse Rec8 at three positions in vitro, but only when Rec8 is hyper-phosphorylated. Expression of a non-cleavable Rec8 variant (Rec8-N) in male mice abolishes the first meiotic division, producing secondary spermatocytes with 4C DNA content. In oocytes, Rec8-N causes asynchronous and delayed chromosome segregation during anaphase I. In vitro separase cleavage assay, non-cleavable Rec8 transgenic mouse, chromosome spread analysis, flow cytometry Journal of cell science High 19625504
2009 Rec8 guides the distribution of Spo11 along yeast meiotic chromosomes. Spo11 binds to Rec8-binding sites during premeiotic S phase, and deletion of REC8 alters Spo11 localization at centromeres and specific chromosomal arm intervals, causing region-specific loss of DSB formation. Genome-wide chromatin immunoprecipitation (ChIP) on tiling arrays, rec8 deletion analysis Molecular biology of the cell High 19439448
2010 Casein kinase 1delta/epsilon (CK1delta/epsilon) and Dbf4-dependent Cdc7 kinase (DDK) phosphorylate multiple sites on Rec8, and both kinases are required for Rec8 cleavage by separase and meiosis I nuclear division in budding yeast. PP2A (recruited by shugoshin) protects centromeric cohesion by opposing CK1delta/epsilon- and DDK-dependent phosphorylation of Rec8. Phosphomimetic Rec8 mutations bypass shugoshin protection at centromeres. Kinase inhibition (genetic and chemical), phosphomimetic and phospho-null Rec8 mutants, meiotic division analysis, in vivo phosphorylation mapping Developmental cell High 20230747
2010 In fission yeast, casein kinase 1 (CK1; Hhp1/Hhp2) acts as the cohesin kinase that phosphorylates Rec8 to promote its separase-mediated cleavage during meiosis I, rather than polo-like kinase. Shugoshin (Sgo1)-PP2A counteracts this phosphorylation to protect centromeric Rec8. Forced localization of excess Hhp2 at pericentromeres abrogates Sgo1-PP2A protection, establishing that the balance between Rec8 phosphorylation by CK1 and dephosphorylation by Sgo1-PP2A regulates stepwise cohesion loss. Genetic screen ('anti-shugoshin' screen), targeted gene perturbation, forced localization experiments, Rec8 cleavage assays Nature cell biology High 20383139
2010 Rec8-containing cohesin maintains bivalent chromosomes without detectable turnover during the oocyte growing phase. TEV protease cleavage of Rec8 (via a Rec8-TEV allele) triggers chiasmata resolution at meiosis I and sister centromere disjunction at meiosis II. Ectopic Rec8 activation during the growing phase does not rebuild cohesion, demonstrating the absence of cohesin turnover in oocytes. TEV-cleavable Rec8 knockin mouse, TEV protease microinjection, confocal live-cell imaging, conditional transgene activation Genes & development High 20971813
2010 In fission yeast, CK1 isoforms Hhp1 and Hhp2 are required for full levels of Rec8 phosphorylation (mapped by mass spectrometry) and for efficient separase-mediated removal of Rec8 at anaphase I onset. Rec8 phosphorylation is required for proper chromosome disjunction during meiosis. Mass spectrometry phosphorylation mapping, CK1 mutant analysis, Rec8 removal quantification Cell cycle (Georgetown, Tex.) High 20581463
2014 STAG3 stabilizes REC8-containing cohesin complexes during meiosis. In Stag3 hypomorphic mice with severely reduced STAG3, REC8 cohesin complex stability is reduced, causing defects in chromosome axis compaction, synapsis, and recombination. STAG3-REC8 cohesin complexes are specifically required for meiotic chromosome structure and function. Stag3 hypomorphic knockin mouse, immunofluorescence, chromosome spread analysis, cohesin complex quantification The EMBO journal High 24797475
2016 Rec8-containing cohesin established during fetal oocyte DNA replication is maintained without detectable turnover throughout months of dictyate arrest. Rec8 activated in arrested oocytes does not establish new cohesion (detected by TEV cleavage and live imaging), demonstrating that cohesion renewal cannot occur post-replicatively in arrested mouse oocytes. Tamoxifen-inducible Cre for conditional Rec8 activation, TEV protease cleavage assay, live-cell imaging Current biology : CB High 26898469
2016 The separase-cleaved C-terminal fragment of mammalian Rec8 bears an N-terminal Glu residue and is degraded by the N-end rule pathway via Ate1 arginyltransferase-mediated N-terminal arginylation followed by proteasomal degradation. Male Ate1 conditional knockout mice are nearly infertile due to massive spermatocyte apoptosis during meiosis I metaphase, caused by failure to destroy the Rec8 C-terminal fragment. Germ-cell-confined Ate1 conditional knockout mouse, in vivo Rec8 fragment detection, protein half-life assay, N-end rule pathway analysis The Journal of biological chemistry High 26858254
2016 High density of REC8 cohesin complexes along sister chromatid axes (separated by <15% of total axis length) prevents local axis separation and illegitimate synaptonemal complex formation between sister chromatids. REC8 but not RAD21L or RAD21 flanks sites of local separated axial elements (LSAEs), and reduced cohesin levels cause both LSAEs and inter-sister SC formation at REC8-free regions. Super-resolution microscopy (STED), Stag3 hypomorphic mutant with reduced cohesin, quantitative cohesin distribution analysis EMBO reports High 27170622
2016 During meiotic prophase in budding yeast, Rec8 phosphorylation (at 6, 24, or 29 sites with alanine substitutions) does not affect axis formation or recombination initiation/non-crossover recombination, but is specifically required for crossover-related events. DDK (Dbf4-dependent Cdc7 kinase) inhibition at defined times recapitulates these defects, while Hrr25/CK1 or Polo-like kinase inhibition does not, establishing DDK as the key kinase for Rec8's prophase role in crossover control. Rec8 phospho-mutant analysis (progressive alanine substitutions), timed kinase inhibition, crossover frequency and distribution assays Nucleic acids research High 27484478
2018 Rec8 cohesin requires STAG3 (but not STAG1 or STAG2) for nuclear entry, chromatin loading, and functional sister chromatid cohesion in somatic cells. Rec8-STAG3 cohesin physically interacts with Pds5, Wapl, and sororin, is susceptible to Wapl-dependent ring opening (cohesion dissolution), and is protected by sororin — demonstrating that meiotic Rec8 cohesin is regulated by the same Wapl/sororin mechanism as mitotic cohesin. Ectopic expression in HEK293 cells, co-immunoprecipitation, chromatin loading assay, Wapl/sororin knockdown Journal of cell science High 29724914
2018 Meiosis-specific cohesin component Rec8 binds to Mps3 (a SUN-domain nuclear envelope protein) during meiosis in budding yeast and controls Mps3 localization and dynamics on the nuclear envelope. Ectopic expression of Rec8 in mitotic cells induces formation of Mps3 patches/foci on the nuclear envelope, and this requires the cohesin regulator Rad61/Wpl1. Co-immunoprecipitation, ectopic Rec8 expression in mitotic yeast, nuclear envelope localization assays, Wpl1 epistasis Genes to cells Medium 30417519
2020 EWSR1 binds to both PRDM9 and phosphorylated REC8 (pREC8) in male meiotic cells. Conditional knockout of Ewsr1 causes meiotic arrest with decreased histone trimethylation at meiotic hotspots, impaired DSB repair, and reduced crossover number, suggesting EWSR1 links PRDM9-bound hotspots to the chromosome axis through pREC8. Co-immunoprecipitation, Ewsr1 conditional knockout mouse, ChIP analysis for histone methylation, crossover quantification Molecular biology of the cell Medium 33175657
2020 Genome-wide ChIP-seq in Arabidopsis shows REC8 associates with high-nucleosome-occupancy regions in multiple chromatin states (H3K4me, H3K27me, H3K9me). REC8 enrichment suppresses meiotic DSBs and crossovers at both chromosome and fine scales. In rec8 mutants, abnormal axis structures recruit DSB-associated foci and undergo synapsis followed by chromosome fragmentation. ChIP-seq (REC8), rec8 mutant analysis, kyp suvh5 suvh6 mutant ChIP-seq, immunofluorescence The Plant cell Medium 32024691
2021 Cleavage of REC8 by Separase at meiosis I is necessary and sufficient to convert sister kinetochores from co-orientation to bi-orientation, and to deprotect pericentromeric cohesion. Transfer of spindle-chromosome complexes between meiosis I and II showed both co-orientation and pericentromeric cohesin protection depend on the chromosomal context (not cytoplasm). Selective REC8 cleavage near kinetochores is sufficient to destroy co-orientation in univalent chromosomes. Spindle-chromosome complex (SCC) transfer between meiosis I and II oocytes, separase catalytic mutant, selective REC8 cleavage experiments, live imaging Developmental cell High 34758289
2021 Two foundational meiotic proteins, Spo11 and Rec8, can dismantle centromeres via nucleosome remodeling factors. Overexpression of Rec8 in proliferating fission yeast or human cells leads to loss of mitotic kinetochores, demonstrating that Rec8 can destabilize centromeric chromatin when expressed ectopically. Rec8 overexpression in fission yeast and human cells, centromere marker loss assay, telomere bouquet mutant analysis Nature Medium 33658710
2021 Meikin (Moa1 in fission yeast) associates with Plo1 (polo-like kinase) and synergizes with shugoshin (Sgo1) to protect centromeric Rec8 cohesion during meiosis I. Moa1-Plo1 phosphorylates Rec8 at a key site, which potentiates PP2A activity associated with Sgo1, leading to dephosphorylation of Rec8 at a separase-promoting site and thus preventing Rec8 cleavage. Genetic analysis of moa1 mutants, Plo1 kinase assays, Rec8 phosphorylation site mapping, epistasis with sgo1-PP2A pathway Genes & development High 33888556
2021 Rec8 regulates chromosome axis length by modulating Pds5 protein, while Pds5 in turn regulates axis length and crossover frequency in a dosage-dependent manner. Pds5 depletion does not alter Rec8 abundance, but Rec8 affects Pds5, placing Rec8 upstream of Pds5 in axis length control. Pds5 and Rec8 protein quantification, chromosome axis length measurement, crossover frequency analysis, epistasis Science advances Medium 33712462
2022 Aurora B/C kinase activities promote Rec8 phosphorylation in mammalian oocytes, and this phosphorylation is required for Rec8 cleavage by separase at meiosis I. A specific Rec8 phosphorylation site was identified that is phosphorylated in vivo; inhibition of Aurora B/C during meiotic maturation impairs both Rec8 phosphorylation and chromosome segregation. Rec8-cleavage biosensor in single mouse oocytes (live imaging), phosphomutant analysis, Aurora B/C kinase inhibition, endogenous Rec8 phosphorylation assay Current biology : CB High 35385691
2022 MicroRNA miR-202 safeguards meiotic progression by repressing SEPARASE mRNA, thereby maintaining REC8 protein levels. Loss of miR-202 causes premature Separase-mediated REC8 cleavage, resulting in spermatocyte apoptosis and disruption of the zygotene-to-pachytene transition. miR-202 knockout mouse, target validation (Separase as miR-202 target), REC8 protein quantification, meiotic chromosome analysis EMBO reports Medium 35712867
2023 Meiotic DSBs regulate cleavage-independent dissociation of Rec8-cohesin from chromosomes during meiotic prophase I in budding yeast. Genome-wide Rec8 binding analysis shows its distribution changes from mid to late prophase I with cleavage-independent loss. The spo11 mutant (lacking meiotic DSBs) does not show this redistribution, demonstrating DSBs drive a cohesin remodeling pathway distinct from separase cleavage. Genome-wide ChIP-seq for Rec8, spo11 mutant analysis, meiotic prophase stage fractionation Genes to cells Medium 37968127
2024 Phosphorylation of Rec8 at specific Plo1 (polo-like kinase) phosphorylation sites, identified through meikin (Moa1) association, is required for monopolar orientation of sister kinetochores in meiosis I in fission yeast. Non-phosphorylatable mutations at these sites (in Rec8 and Psm3) show specific mono-orientation defects, genetically separating this function from cohesion protection. Plo1 phosphorylation site identification, non-phosphorylatable Rec8/Psm3 mutants, kinetochore orientation assay in fission yeast Life science alliance High 38448160
2024 Acetylation of Rec8 cohesin complexes at Psm3-K1013 by Eso1 acetyltransferase is required for reductional chromosome segregation in meiosis. This acetylation is largely dependent on the meiotic kinetochore factor meikin (Moa1) and cooperates with canonical acetylation at Psm3-K105 and K106. Meiosis-specific Rec8 cohesin complexes localized at centromeres were purified and analyzed by mass spectrometry. Purification of meiotic centromeric Rec8 cohesin complexes, mass spectrometry identification of acetylation, Psm3 acetylation-site mutants, chromosome segregation analysis Life science alliance High 38575358
2006 Securin degradation via the ubiquitin-proteasome pathway is required for Rec8 proteolysis at the metaphase-to-anaphase transition in mouse and pig oocytes. Inhibition of the ubiquitin-proteasome pathway blocks both securin and Rec8 degradation. Microinjection of securin antibody into MII oocytes leads to Rec8 degradation, placing securin upstream of Rec8 in the meiotic metaphase-to-anaphase pathway. Proteasome inhibitor treatment, securin antibody microinjection, Western blot for securin and Rec8, immunofluorescence in mouse/pig oocytes Frontiers in bioscience Medium 16720305
2016 Meiotic cohesin subunits RAD21L and REC8 localize at distinct positions within the synaptonemal complex: both at connection sites between lateral elements and transverse filaments in pachynema, with RAD21L positioned interior to REC8. Some RAD21L but not REC8 signals appear to bridge unsynapsed regions in zygonema, and recombination intermediate signals overlap more with RAD21L than REC8. Super-resolution microscopy (3D-SIM), immunofluorescence in mouse spermatocytes, recombination marker co-localization The Journal of reproduction and development Medium 27665783
2013 Nociceptin (a neuropeptide) induces rapid Rec8 phosphorylation in mouse spermatocytes through its receptor Oprl-1, which is exclusively expressed in the plasma membrane of testicular germ cells. In vivo injection of nociceptin stimulates Rec8 phosphorylation and meiotic chromosome dynamics; nocistatin (a nociceptin inhibitor) abolishes these effects. In vivo nociceptin/nocistatin injection, Rec8 phosphorylation assay (Western blot), Oprl-1 receptor localization Endocrinology Medium 23720425
2022 REC8 interacts with MAVS and STING in the cytoplasm during viral infection and inhibits their K48-linked ubiquitination by RNF5, thereby stabilizing these innate immune signaling proteins. SUMOylated REC8 translocates from nucleus to cytoplasm upon viral infection (triggered via JAK-STAT pathway upregulation). REC8 also promotes recruitment of TBK1 to MAVS and STING, enhancing interferon signaling. Co-immunoprecipitation, ubiquitination assay, REC8 knockdown (siRNA), viral infection assay (VSV, NDV, HSV), subcellular fractionation, SUMO modification analysis Journal of virology Medium 35107381
2025 Moa1 (meikin) and Sgo1 (shugoshin) are degraded during anaphase I by the APC/C-Slp1 pathway in fission yeast. Non-degradable Moa1 and Sgo1 expressed in meiosis II can protect Rec8 cohesin; the localization of Sgo1 and phosphorylation of Rec8 at S449 and S450 are necessary and sufficient to protect Rec8 during meiosis II. Non-degradable Moa1/Sgo1 mutant expression in meiosis II, Rec8 phosphosite mutants, APC/C genetic analysis bioRxivpreprint Medium bio_10.1101_2025.09.19.677360

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Cohesin Rec8 is required for reductional chromosome segregation at meiosis. Nature 446 10440376
2005 Absence of mouse REC8 cohesin promotes synapsis of sister chromatids in meiosis. Developmental cell 262 15935783
2003 Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1beta and SMC3. The Journal of cell biology 226 12615909
2010 Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes. Genes & development 213 20971813
1999 Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of the Rad21p family conserved from fission yeast to humans. Molecular and cellular biology 204 10207075
2000 Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p. Genes & development 178 10691741
1995 The rec8 gene of Schizosaccharomyces pombe is involved in linear element formation, chromosome pairing and sister-chromatid cohesion during meiosis. Genetics 172 8536990
1999 The DIF1 gene of Arabidopsis is required for meiotic chromosome segregation and belongs to the REC8/RAD21 cohesin gene family. The Plant journal : for cell and molecular biology 165 10504568
2010 Rec8 phosphorylation by casein kinase 1 and Cdc7-Dbf4 kinase regulates cohesin cleavage by separase during meiosis. Developmental cell 150 20230747
2004 Positional cloning and characterization of mouse mei8, a disrupted allelle of the meiotic cohesin Rec8. Genesis (New York, N.Y. : 2000) 145 15515002
2003 Temporally and spatially selective loss of Rec8 protein from meiotic chromosomes during mammalian meiosis. Journal of cell science 139 12759374
2010 Shugoshin-PP2A counteracts casein-kinase-1-dependent cleavage of Rec8 by separase. Nature cell biology 133 20383139
2006 Alleles of afd1 dissect REC8 functions during meiotic prophase I. Journal of cell science 119 16868028
2006 Rec8 phosphorylation and recombination promote the step-wise loss of cohesins in meiosis. Nature 118 16672979
2003 Rec8 cleavage by separase is required for meiotic nuclear divisions in fission yeast. The EMBO journal 113 14532136
2016 Chromosome Cohesion Established by Rec8-Cohesin in Fetal Oocytes Is Maintained without Detectable Turnover in Oocytes Arrested for Months in Mice. Current biology : CB 96 26898469
2009 Rec8 guides canonical Spo11 distribution along yeast meiotic chromosomes. Molecular biology of the cell 92 19439448
2010 Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes. Human reproduction (Oxford, England) 89 20634189
2009 Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. Journal of cell science 85 19625504
2014 STAG3-mediated stabilization of REC8 cohesin complexes promotes chromosome synapsis during meiosis. The EMBO journal 83 24797475
2005 A REC8-dependent plant Shugoshin is required for maintenance of centromeric cohesion during meiosis and has no mitotic functions. Current biology : CB 70 15916952
2010 Casein kinase 1 is required for efficient removal of Rec8 during meiosis I. Cell cycle (Georgetown, Tex.) 67 20581463
2006 The rice OsRad21-4, an orthologue of yeast Rec8 protein, is required for efficient meiosis. Plant molecular biology 67 16525890
2016 Meiotic prophase roles of Rec8 in crossover recombination and chromosome structure. Nucleic acids research 55 27484478
2009 The role of meiotic cohesin REC8 in chromosome segregation in gamma irradiation-induced endopolyploid tumour cells. Experimental cell research 55 19463812
1999 Meiotic chromosome dynamics dependent upon the rec8(+), rec10(+) and rec11(+) genes of the fission yeast Schizosaccharomyces pombe. Genetics 55 10471700
2020 Interacting Genomic Landscapes of REC8-Cohesin, Chromatin, and Meiotic Recombination in Arabidopsis. The Plant cell 52 32024691
2006 Loss of Rec8 from chromosome arm and centromere region is required for homologous chromosome separation and sister chromatid separation, respectively, in mammalian meiosis. Cell cycle (Georgetown, Tex.) 51 16855401
1992 Meiotically induced rec7 and rec8 genes of Schizosaccharomyces pombe. Genetics 49 1339382
2001 Cloning and characterization of two Arabidopsis genes that belong to the RAD21/REC8 family of chromosome cohesin proteins. Gene 48 11410371
2016 Genetic Interactions Between the Meiosis-Specific Cohesin Components, STAG3, REC8, and RAD21L. G3 (Bethesda, Md.) 46 27172213
2016 REC8 functions as a tumor suppressor and is epigenetically downregulated in gastric cancer, especially in EBV-positive subtype. Oncogene 41 27212034
2018 A Genomic Region Containing REC8 and RNF212B Is Associated with Individual Recombination Rate Variation in a Wild Population of Red Deer (Cervus elaphus). G3 (Bethesda, Md.) 37 29764960
2010 Mek1 suppression of meiotic double-strand break repair is specific to sister chromatids, chromosome autonomous and independent of Rec8 cohesin complexes. Genetics 37 20421598
2021 Meiotic genes in premature ovarian insufficiency: variants in HROB and REC8 as likely genetic causes. European journal of human genetics : EJHG 36 34707299
2012 The spread of a transposon insertion in Rec8 is associated with obligate asexuality in Daphnia. Proceedings of the National Academy of Sciences of the United States of America 33 22215604
2016 High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation. EMBO reports 32 27170622
2018 REC8 inhibits EMT by downregulating EGR1 in gastric cancer cells. Oncology reports 27 29393474
2022 Rec8 Cohesin: A Structural Platform for Shaping the Meiotic Chromosomes. Genes 26 35205245
2021 Loss of sister kinetochore co-orientation and peri-centromeric cohesin protection after meiosis I depends on cleavage of centromeric REC8. Developmental cell 26 34758289
2021 Interplay between Pds5 and Rec8 in regulating chromosome axis length and crossover frequency. Science advances 25 33712462
2015 REC8 is a novel tumor suppressor gene epigenetically robustly targeted by the PI3K pathway in thyroid cancer. Oncotarget 25 26472282
2002 Analyses of mRNA expression patterns of cohesin subunits Rad21 and Rec8 in mice: germ cell-specific expression of rec8 mRNA in both male and female mice. Zoological science 25 12130806
2016 Meiotic cohesin subunits RAD21L and REC8 are positioned at distinct regions between lateral elements and transverse filaments in the synaptonemal complex of mouse spermatocytes. The Journal of reproduction and development 23 27665783
2022 Aurora B/C-dependent phosphorylation promotes Rec8 cleavage in mammalian oocytes. Current biology : CB 21 35385691
2021 Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8. Nature 21 33658710
2016 Degradation of the Separase-cleaved Rec8, a Meiotic Cohesin Subunit, by the N-end Rule Pathway. The Journal of biological chemistry 21 26858254
2018 Studying meiotic cohesin in somatic cells reveals that Rec8-containing cohesin requires Stag3 to function and is regulated by Wapl and sororin. Journal of cell science 18 29724914
2022 MicroRNA-202 safeguards meiotic progression by preventing premature SEPARASE-mediated REC8 cleavage. EMBO reports 17 35712867
2020 REC8 suppresses tumor angiogenesis by inhibition of NF-κB-mediated vascular endothelial growth factor expression in gastric cancer cells. Biological research 16 32958054
2020 EWSR1 affects PRDM9-dependent histone 3 methylation and provides a link between recombination hotspots and the chromosome axis protein REC8. Molecular biology of the cell 15 33175657
2006 Degradation of securin in mouse and pig oocytes is dependent on ubiquitin-proteasome pathway and is required for proteolysis of the cohesion subunit, Rec8, at the metaphase-to-anaphase transition. Frontiers in bioscience : a journal and virtual library 15 16720305
2022 The meiotic cohesin subunit REC8 contributes to multigenic adaptive evolution of autopolyploid meiosis in Arabidopsis arenosa. PLoS genetics 14 35830475
2021 Meikin synergizes with shugoshin to protect cohesin Rec8 during meiosis I. Genes & development 13 33888556
1999 Centromere mapping functions for aneuploid meiotic products: Analysis of rec8, rec10 and rec11 mutants of the fission yeast Schizosaccharomyces pombe. Genetics 13 10471699
2021 REC8 promotes tumor migration, invasion and angiogenesis by targeting the PKA pathway in hepatocellular carcinoma. Clinical and experimental medicine 12 33677646
2021 REC8 enhances stemness and promotes metastasis of colorectal cancer through BTK/Akt/β-catenin signaling pathway. Translational oncology 12 34890967
2022 The Role of REC8 in the Innate Immune Response to Viral Infection. Journal of virology 11 35107381
2015 Unique subcellular distribution of phosphorylated Plk1 (Ser137 and Thr210) in mouse oocytes during meiotic division and pPlk1(Ser137) involvement in spindle formation and REC8 cleavage. Cell cycle (Georgetown, Tex.) 11 26654596
2022 REC8 inhibits proliferation, migration and invasion of breast cancer cells by targeting CDC20. Molecular medicine reports 10 35616161
2022 Disruption of REC8 in Meiosis I led to watermelon seedless. Plant science : an international journal of experimental plant biology 8 35905897
2018 Cloning and characterization of the homoeologous genes for the Rec8-like meiotic cohesin in polyploid wheat. BMC plant biology 8 30305022
2018 Meiosis-specific cohesin component, Rec8, promotes the localization of Mps3 SUN domain protein on the nuclear envelope. Genes to cells : devoted to molecular & cellular mechanisms 8 30417519
2016 The cohesin REC8 prevents illegitimate inter-sister synaptonemal complex assembly. EMBO reports 8 27170621
2013 Nociceptin induces Rec8 phosphorylation and meiosis in postnatal murine testes. Endocrinology 8 23720425
2008 Analysis of the meiotic recombination gene REC8 for sequence variations in a population with severe male factor infertility. Systems biology in reproductive medicine 8 18570052
2021 Cloning and characterization of rec8 gene in orange-spotted grouper (Epinephelus coioides) and Dmrt1 regulation of rec8 promoter activity. Fish physiology and biochemistry 6 33547601
2020 In vitro effects of androgen on testicular development by the AR-foxl3-rec8/fbxo47 axis in orange-spotted grouper (Epinephelus coioides). General and comparative endocrinology 6 32057909
2018 Retinoic acid-induced CYP51 nuclear translocation promotes meiosis prophase I process and is correlated to the expression of REC8 and STAG3 in mice. Biology open 6 30420384
2021 Differential expression patterns of the two paralogous Rec8 from Nile tilapia and their responsiveness to retinoic acid signaling. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 5 33482354
2014 Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in S. cerevisiae. Frontiers in genetics 5 25136348
2024 Phosphorylation of Rec8 cohesin complexes regulates mono-orientation of kinetochores in meiosis I. Life science alliance 3 38448160
2023 DNA double-strand breaks regulate the cleavage-independent release of Rec8-cohesin during yeast meiosis. Genes to cells : devoted to molecular & cellular mechanisms 3 37968127
2022 Liposome-Encapsulated Rec8 and Dmrt1 Plasmids Induce Red-Spotted Grouper (Epinephelus akaara) Testis Maturation. Marine biotechnology (New York, N.Y.) 3 35303207
2022 TOP-2 is differentially required for the proper maintenance of the cohesin subunit REC-8 on meiotic chromosomes in Caenorhabditis elegans spermatogenesis and oogenesis. Genetics 3 35951744
2018 Loss of Cohesin Subunit Rec8 Switches Rad51 Mediator Dependence in Resistance to Formaldehyde Toxicity in Ustilago maydis. Genetics 3 30082279
2024 Acetylation of Rec8 cohesin complexes regulates reductional chromosome segregation in meiosis. Life science alliance 1 38575358
2026 The dynamic pool of Rec8-cohesin is crucial for meiotic recombination and transcription regulation in the yeast S. cerevisiae. The Journal of biological chemistry 0 42036042
2025 CpG site methylation regulates mouse Rec8 gene promoter activity. The Journal of reproduction and development 0 40189260
2025 REC8-Cohesin Preferentially Localizes to Promoters of Genes that are Regulated by Transcription Suppressor BEND2 During Early Meiosis. Genomics, proteomics & bioinformatics 0 41476252
2024 Functional roles of the interaction of Moa1 with CENP-C and Rec8 in meiosis of Schizosaccharomyces pombe. Yi chuan = Hereditas 0 39140145
2023 Analysis of absolute amounts of two meiotic cohesin subunits, RAD21L and REC8, in mouse spermatocytes. The Journal of reproduction and development 0 36740274
2023 Genome-Wide Analysis of the Rad21/REC8 Gene Family in Cotton (Gossypium spp.). Genes 0 37239353
2023 REC8 regulates neuroblastoma cell proliferation, migration, invasion, and angiogenesis via STAT3/VEGF signaling. Journal of the Egyptian National Cancer Institute 0 38105365
2022 Protocol to measure cleavage efficiency of the meiotic cohesin subunit Rec8 by separase in mouse oocytes using a biosensor. STAR protocols 0 36149797