Affinage

REC8

Meiotic recombination protein REC8 homolog · UniProt O95072

Length
547 aa
Mass
62.6 kDa
Annotated
2026-06-10
81 papers in source corpus 35 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

REC8 is the meiosis-specific α-kleisin subunit of cohesin that mediates sister-chromatid cohesion and organizes the meiotic chromosome axis, and whose regulated cleavage drives the two-step chromosome segregation of meiosis (PMID:10440376, PMID:12759374, PMID:14532136). Loss of REC8 causes premature sister separation and equational rather than reductional segregation at meiosis I, establishing its core role in maintaining cohesion and orienting sister kinetochores for co-segregation (PMID:10440376). In mammals, REC8 assembles with SMC1β, SMC3 and the stromalin STAG3 into a meiosis-specific cohesin; STAG3 stabilizes REC8 and is necessary and sufficient to license REC8 chromatin loading and cohesion activity, even ectopically in somatic cells where REC8-STAG3 engages PDS5, WAPL and sororin (PMID:12759374, PMID:24797475, PMID:29724914). REC8 is laid down before other cohesin and axial-element proteins to scaffold axial/lateral element assembly, and a high density of REC8 along sister axes restricts synaptonemal complex formation to between homologs rather than between sisters (PMID:12615909, PMID:15935783, PMID:27170622); it further patterns Spo11-dependent DSB distribution and supports crossover formation (PMID:19439448, PMID:27484478). Stepwise cohesion loss is controlled by phosphoregulation: casein kinase 1 (CK1δ/ε) and DDK phosphorylate REC8 to license separase cleavage, first on chromosome arms to resolve chiasmata at meiosis I and later at centromeres at meiosis II (PMID:14532136, PMID:19625504, PMID:20230747, PMID:20581463), while centromeric REC8 is protected by shugoshin-PP2A opposing these kinases, a protection potentiated by meikin-Polo kinase phosphorylation of REC8 at S450/S449 (PMID:20383139, PMID:33888556). In mammalian oocytes Aurora B/C phosphorylates REC8 to promote its cleavage, and cohesin established during fetal DNA replication persists without turnover through prolonged dictyate arrest (PMID:20971813, PMID:26898469, PMID:35385691). The separase-generated C-terminal REC8 fragment is destroyed via N-terminal arginylation by Ate1 and the N-end rule pathway, a step required for spermatocyte survival (PMID:26858254). Beyond meiosis, REC8 has been implicated in cytoplasmic stabilization of MAVS/STING innate immune signaling (PMID:35107381).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Established that the rec8 gene product is required for the integrated meiotic program—axial core formation, homolog pairing, and sister cohesion—defining it as a central organizer rather than a single-task factor.

    Evidence Genetic and cytological analysis of the rec8-110 mutant in fission yeast

    PMID:8536990

    Open questions at the time
    • Molecular identity of Rec8 as a cohesin subunit not yet defined
    • No protein-level or biochemical characterization
  2. 1999 High

    Defined Rec8 as a meiosis-specific cohesin whose persistence at centromeres through meiosis I and loss at anaphase II underlies reductional segregation, answering how sisters co-segregate at MI.

    Evidence Gene deletion, immunolocalization and in situ hybridization in fission yeast; cloning of human REC8

    PMID:10207075 PMID:10440376

    Open questions at the time
    • Mechanism of differential arm vs. centromere cohesion loss unknown
    • Phosphorylation function not yet linked to cleavage
  3. 2000 Medium

    Showed Rec8 feeds back on meiotic S-phase progression, linking cohesion establishment to replication timing.

    Evidence REC8 deletion and S-phase length measurement in budding yeast

    PMID:10691741

    Open questions at the time
    • Molecular basis of S-phase coordination unresolved
    • Single genetic background
  4. 2003 High

    Established the mammalian REC8 cohesin composition (SMC1β/SMC3, with SCP3 association) and demonstrated that REC8 is incorporated first to scaffold axial element assembly and is lost stepwise from arms then centromeres.

    Evidence Immunoprecipitation, immunofluorescence staging and co-IP in rat and mouse meiocytes

    PMID:12615909 PMID:12759374

    Open questions at the time
    • STAG3 not yet identified as the meiotic stromalin partner
    • Functional consequence of RAD51/DMC1 co-IP unestablished
  5. 2003 High

    Demonstrated that separase cleavage of Rec8 is required for segregation, with distinct arm vs. centromere complexes resolved at MI vs MII—the molecular basis of two-step segregation.

    Evidence Non-cleavable Rec8 mutant and Rec11 depletion in fission yeast

    PMID:14532136

    Open questions at the time
    • Kinases licensing cleavage not yet identified
    • Protection mechanism at centromeres undefined
  6. 2005 High

    Defined a major mammalian REC8 function as restricting synapsis to homologs, since its loss causes inter-sister synapsis and sterility.

    Evidence Rec8 knockout mouse cytology in both sexes

    PMID:15935783

    Open questions at the time
    • Quantitative axis-density requirement not addressed
    • Recombination/DSB phenotype not detailed
  7. 2006 High

    Showed Rec8 phosphorylation cooperates with shugoshin and recombination to set the stepwise cohesion-removal pattern, and confirmed in oocytes that arm vs. centromeric Rec8 loss drives MI vs MII separation.

    Evidence Phosphomutant analysis with Sgo1/recombination genetics in budding yeast; anti-Rec8 antibody microinjection in mouse oocytes

    PMID:16672979 PMID:16855401

    Open questions at the time
    • Specific kinases not yet pinned down
    • Antibody microinjection lacks site resolution
  8. 2009 High

    Reconstituted that separase cleaves Rec8 only when hyper-phosphorylated and showed cleavage is required in vivo for chiasma resolution, coupling phosphoregulation directly to cleavage.

    Evidence In vitro cleavage assay and non-cleavable Rec8 transgenic mice; ChIP tiling of Spo11/Rec8 in budding yeast

    PMID:19439448 PMID:19625504

    Open questions at the time
    • Identity of the relevant in vivo kinase(s) still open
    • Mechanism of Rec8-directed Spo11 prearrangement unresolved
  9. 2010 High

    Identified CK1δ/ε and DDK as the cohesin kinases licensing Rec8 cleavage and established that PP2A protects centromeric Rec8 by opposing these phosphorylations—resolving the kinase/phosphatase logic of stepwise cohesion loss.

    Evidence Phosphomutant/phosphomimetic and kinase-inhibition analyses with MS site mapping in budding and fission yeast

    PMID:20230747 PMID:20383139 PMID:20581463

    Open questions at the time
    • Polo-like kinase role reassigned but its meiotic contribution remained to be reconciled
    • How site-specific phosphorylation is spatially controlled unclear
  10. 2010 High

    Demonstrated by TEV-cleavable knock-in that Rec8 cohesin holds bivalents from birth to ovulation, does not turn over, and is exchanged for Scc1 cohesin at fertilization.

    Evidence TEV-cleavable Rec8/Scc1 knock-in mice with TEV microinjection and live imaging in oocytes

    PMID:20971813

    Open questions at the time
    • Why arrested-oocyte cohesin cannot be renewed not yet explained
  11. 2014 High

    Identified STAG3 as the stromalin that stabilizes REC8 cohesin and is required for axis compaction, synapsis, and recombination.

    Evidence Hypomorphic Stag3 mouse with cohesin dosage and meiotic phenotype analysis

    PMID:24797475

    Open questions at the time
    • Sufficiency of STAG3 for REC8 function not yet shown
    • Stoichiometry of the complex undefined
  12. 2016 High

    Resolved the cohesion lifecycle and axis-density logic: cohesion establishment requires ongoing fetal DNA replication, and high REC8 axis density prevents ectopic inter-sister SC; also revealed a cleavage-independent prophase role of DDK phosphorylation in crossover formation.

    Evidence Inducible Rec8 transgene with TEV readout, super-resolution imaging of hypomorphic Stag3 meiocytes, and phospho-alanine Rec8 series in budding yeast

    PMID:26898469 PMID:27170622 PMID:27484478 PMID:27665783

    Open questions at the time
    • Replication-coupled establishment mechanism not molecularly defined
    • How DDK phosphorylation promotes crossovers without cleavage unknown
  13. 2016 High

    Established that the separase-generated C-terminal Rec8 fragment is destroyed by Ate1 arginylation via the N-end rule, a step essential for spermatocyte survival at metaphase I.

    Evidence Germ-cell-specific Ate1 knockout mouse with biochemical fragment-stability analysis

    PMID:26858254

    Open questions at the time
    • Why fragment persistence is lethal mechanistically unclear
    • Female meiosis dependence not addressed
  14. 2018 High

    Demonstrated STAG3 is sufficient to drive REC8 nuclear import, chromatin loading and cohesion in somatic cells, and that REC8-STAG3 obeys WAPL/sororin regulation; also linked Rec8 to the SUN protein Mps3 at the nuclear envelope.

    Evidence Ectopic expression, chromatin fractionation and co-IP in HEK293; co-IP and ectopic expression in budding yeast

    PMID:29724914 PMID:30417519

    Open questions at the time
    • Physiological role of Rec8-Mps3 tethering in meiosis not established
    • WAPL/sororin regulation in true meiocytes not directly tested
  15. 2020 Medium

    Connected REC8 to recombination hotspot positioning by showing EWSR1 bridges PRDM9-marked hotspots to phosphorylated REC8 on the axis.

    Evidence Co-IP of EWSR1 with PRDM9 and pREC8 plus conditional Ewsr1 KO and ChIP-seq in mouse

    PMID:33175657

    Open questions at the time
    • Direct vs. indirect EWSR1-pREC8 interaction unresolved
    • Single lab without reciprocal validation in meiocytes
  16. 2021 High

    Established that pericentromeric REC8 cleavage at MI both converts sister kinetochores to bi-orientation and deprotects centromeric cohesion; identified meikin-Plo1 phosphorylation of Rec8 that potentiates Sgo1-PP2A protection; and revealed a gain-of-function capacity of Rec8 to dismantle mitotic centromeres.

    Evidence Spindle-chromosome transfers with site-specific TEV cleavage in oocytes; phospho-site epistasis in fission yeast; Rec8 overexpression in fission yeast and human cells

    PMID:33658710 PMID:33888556 PMID:34758289

    Open questions at the time
    • How a single cleavage event couples bi-orientation to deprotection mechanistically unclear
    • Physiological relevance of centromere dismantlement in normal meiosis uncertain
  17. 2022 High

    Identified Aurora B/C as the mammalian kinases promoting REC8 cleavage and showed Separase levels are tuned by miR-202 to prevent premature REC8 cleavage; refined fission yeast protection logic to Sgo1/Moa1 turnover and Rec8 S449/S450 phosphorylation.

    Evidence Separase biosensor with phosphomutants and Aurora inhibition in oocytes; miR-202 KO with luciferase target validation; non-degradable Sgo1/Moa1 and phosphomutant analysis in fission yeast (preprint)

    PMID:35385691 PMID:35712867

    Open questions at the time
    • How Aurora B/C activity is spatially restricted to arms vs centromeres unclear
    • Integration of CK1/DDK/Aurora inputs on the same substrate not unified
  18. 2022 Medium

    Reported a non-meiotic cytoplasmic role in which SUMOylated REC8 stabilizes MAVS/STING by blocking RNF5-mediated ubiquitination to support innate antiviral signaling.

    Evidence Co-IP, ubiquitination assays and REC8 knockdown with viral infection in cells

    PMID:35107381

    Open questions at the time
    • Single lab, non-meiotic context not reconciled with germline-restricted expression
    • Reciprocal/in vivo validation lacking
  19. 2024 Medium

    Refined meikin-Plo1 control by dissecting Rec8 phosphosites governing mono-orientation versus cohesion protection, and identified Eso1-dependent meikin-directed acetylation of the cohesin SMC subunit underlying reductional segregation.

    Evidence Non-phosphorylatable Rec8/Psm3 mutants and MS acetylation mapping in fission yeast

    PMID:38448160 PMID:38575358

    Open questions at the time
    • Conservation of these acetylation/phospho events in mammals untested
    • Single-lab findings
  20. 2025 Medium

    Extended REC8 function to chromatin reorganization at the mitosis-to-meiosis transition, localizing to open promoters and interacting with CCNA2, with distribution shaped by BEND2.

    Evidence REC8 ChIP-seq, BEND2 KO, REC8-CCNA2 co-IP and RNA-seq in mouse

    PMID:41476252

    Open questions at the time
    • Direct transcriptional role vs. structural consequence unresolved
    • Functional significance of REC8-CCNA2 interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple kinase inputs (CK1, DDK, Aurora B/C, Polo/meikin) are spatially and temporally integrated on REC8 to achieve precise arm-then-centromere cleavage, and whether the somatic innate-immunity and chromatin/transcription roles represent bona fide non-meiotic functions, remain open.
  • No unified model of combinatorial phosphocode on REC8
  • Non-meiotic roles lack independent confirmation
  • Structural model of meiotic cohesin ring assembly absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0003677 DNA binding 3 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005694 chromosome 4 GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1474165 Reproduction 3 R-HSA-73894 DNA Repair 3 R-HSA-4839726 Chromatin organization 2 R-HSA-168256 Immune System 1
Partners
CCNA2EWSR1MAVSPDS5SMC1BSMC3STAG3WAPL
Complex memberships
REC8-STAG3-PDS5-WAPL-sororin cohesinmeiotic cohesin (REC8-SMC1β-SMC3-STAG3)synaptonemal complex / axial element

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Fission yeast Rec8 is a meiosis-specific cohesin that localizes to centromeres and chromosome arms during pre-meiotic S phase. Centromeric Rec8 persists through meiosis I and is lost at anaphase II. Deletion of rec8 causes premature sister chromatid separation at meiosis I, resulting in equational rather than reductional chromosome segregation, demonstrating that Rec8 maintains sister-chromatid cohesion and orients kinetochores for co-segregation of sisters at meiosis I. Gene deletion, cytological analysis, in situ hybridization, immunolocalization in fission yeast Nature High 10440376
1995 The S. pombe rec8 gene product is required for linear element (axial core) formation, meiotic chromosome pairing, and sister chromatid cohesion. The rec8-110 mutant shows aberrant linear elements, shortened meiotic prophase, impaired homolog pairing, and precocious sister chromatid separation at meiosis I. Genetic analysis of rec8-110 mutant, cytology, in situ hybridization in S. pombe Genetics High 8536990
1999 Fission yeast Rec8p is expressed exclusively during meiosis and localizes to ~100 foci per prophase nucleus. Rec8p exists in an unphosphorylated form early in meiotic prophase and becomes phosphorylated prior to meiosis I (demonstrated using the mei4 mutant blocked before meiosis I). Rec8p persists beyond meiosis I (demonstrated using mes1 mutant blocked before meiosis II). A human ortholog (hREC8) maps to chromosome 14 and is expressed in germ line cells. Western blotting, immunolocalization, analysis of meiotic mutants (mei4, mes1) in S. pombe; cloning of human REC8 Molecular and cellular biology High 10207075
2000 Budding yeast Rec8p modulates meiotic S-phase progression: deletion of REC8 increases S-phase length (~10% in wild-type background; ~30% in spo11Δ background), demonstrating that Rec8p is a key coordinator of meiotic interhomolog and intersister interactions that feeds back on DNA replication progression. Genetic deletion analysis, S-phase length measurement in budding yeast Genes & development Medium 10691741
2003 In rat meiocytes, REC8 appears before premeiotic S phase and forms axial element-like structures (REC8-AEs) before other cohesin subunits (SMC1beta, SMC3) or axial element proteins (SCP2, SCP3) are incorporated, suggesting REC8 provides the initial scaffold for axial element assembly. REC8 persists along chromosome arms until anaphase I and near centromeres until anaphase II, while SMC1beta, SMC3, SCP2, and SCP3 disappear from arms at metaphase I. RAD51 and/or DMC1 co-immunoprecipitates with REC8, suggesting REC8 also provides a basis for recombination complex assembly. Immunofluorescence, co-immunoprecipitation, temporal analysis of protein incorporation into axial elements in rat spermatocytes The Journal of cell biology High 12615909
2003 Mammalian REC8 associates with SMC1beta and SMC3 (but not SMC1alpha) and with synaptonemal complex component SCP3, forming a meiosis-specific cohesin complex. REC8 is selectively lost from chromosome arms at the metaphase I-to-anaphase I transition while persisting at centromeres until anaphase II, providing a molecular basis for the stepwise loss of cohesion in mammalian meiosis. Immunoprecipitation, immunohistochemistry, Western blotting in mouse testis Journal of cell science High 12759374
2003 Separase activation and resultant Rec8 cleavage are required for meiotic chromosome segregation in fission yeast. A non-cleavable form of Rec8 blocks homolog disjunction at meiosis I. Rec8 forms distinct complexes along chromosome arms (with Rec11/SA3) versus centromeres (with Psc3/SA1-SA2), and cleavage of arm Rec8 is required for homolog segregation at meiosis I while centromeric Rec8 cleavage is required for sister segregation at meiosis II. Non-cleavable Rec8 mutant expression, genetic depletion of Rec11, chromosome segregation analysis in S. pombe The EMBO journal High 14532136
2005 Mouse REC8 knockout (both sexes) causes sterility due to germ cell failure. In the absence of REC8, early chromosome pairing appears normal but synapsis occurs between sister chromatids rather than homologs, demonstrating that a major role of REC8 in mammalian meiosis is to restrict synaptonemal complex formation to between homologous chromosomes. Rec8 knockout mouse, cytological analysis of meiotic chromosomes in both sexes Developmental cell High 15935783
2006 In budding yeast, phosphorylation of the cohesin subunit Rec8 contributes to the stepwise removal of cohesin during meiosis. Both Sgo1 (cohesin protector) and meiotic recombination cooperate with Rec8 phosphorylation to establish the meiotic chromosome segregation pattern. Phosphomutant Rec8 analysis, genetic manipulation of Sgo1 and recombination pathways, chromosome spreading in S. cerevisiae Nature High 16672979
2006 In mouse oocytes, loss of arm REC8 (armRec8) is required for homolog separation at meiosis I, while loss of centromeric REC8 (cenRec8) is required for sister chromatid separation at meiosis II. Microinjection of anti-Rec8 antibody into metaphase I oocytes inhibits homolog separation but not polar body emission. Neither loss is required for spindle elongation or cytokinesis. Microinjection of anti-Rec8 antibody into mouse oocytes, immunofluorescence, pharmacological inhibitors Cell cycle (Georgetown, Tex.) Medium 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) causes sterility in male mice with failure of the first meiotic division, demonstrating that Rec8 cleavage by separase is required for chiasma resolution in mammalian meiosis. In vitro cleavage assay with hyper-phosphorylated Rec8, transgenic non-cleavable Rec8 mouse, chromosome spreads, DNA content analysis Journal of cell science High 19625504
2009 In budding yeast, Spo11 initially accumulates around centromeres during premeiotic S phase, then redistributes to chromosome arms where a substantial fraction co-localizes with Rec8 binding sites. Deletion of REC8 alters the distribution of Spo11 at centromeres and specific chromosomal arm intervals, demonstrating that Rec8 prearranges the distribution of Spo11 along meiotic chromosomes to regulate DSB formation. ChIP with high-density tiling arrays (genome-wide Spo11 and Rec8 localization), REC8 deletion analysis in S. cerevisiae Molecular biology of the cell Medium 19439448
2010 Multiple phosphorylation sites within Rec8 and two kinases — casein kinase 1δ/ε (CK1δ/ε) and Dbf4-dependent Cdc7 kinase (DDK) — are required for Rec8 cleavage by separase and meiosis I nuclear division in budding yeast. Rec8 with phosphomimetic mutations is no longer protected from separase at centromeres even when kinases are inhibited. PP2A protects centromeric cohesion by opposing CK1δ/ε- and DDK-dependent phosphorylation of Rec8. Phosphomutant and phosphomimetic Rec8 analysis, kinase inhibition, kinase deletion, meiotic division assays in S. cerevisiae Developmental cell High 20230747
2010 In fission yeast, casein kinase 1 (CK1) ortholog Hhp2 (not Polo-like kinase as previously thought) acts as the cohesin kinase that promotes Rec8 cleavage during meiosis. Forced pericentromeric localization of excess Hhp2 abrogates Sgo1-PP2A protection of centromeric Rec8. The balance between Rec8 phosphorylation by CK1 and dephosphorylation by Sgo1-PP2A regulates the stepwise loss of chromosomal cohesion. Genetic screen for anti-shugoshin factors, forced localization of CK1, phosphorylation analysis, meiotic chromosome segregation assays in S. pombe Nature cell biology High 20383139
2010 Casein kinase 1 (CK1) δ/ε isoforms Hhp1 and Hhp2 are required for full levels of Rec8 phosphorylation and efficient removal of Rec8 at anaphase I onset in fission yeast. Rec8 phosphorylation sites were mapped by mass spectrometry; phosphorylation is required for proper chromosome disjunction. Mass spectrometry phosphorylation site mapping, CK1 mutant analysis, Rec8 phosphorylation quantification in S. pombe Cell cycle (Georgetown, Tex.) High 20581463
2010 Rec8-containing cohesin (dependent on kleisin subunit Rec8) holds bivalent chromosomes together in mouse oocytes from birth until ovulation. TEV protease cleavage of Rec8 (but not Scc1) triggers chiasmata resolution during meiosis I and sister centromere disjunction during meiosis II. There is a dramatic transition from Rec8- to Scc1-containing cohesin at fertilization. Cohesin does not turn over during ≥2 weeks of oocyte growth. TEV-cleavable Rec8 and Scc1 knock-in mice, microinjection of TEV protease into oocytes, confocal live-cell imaging, ectopic Rec8 transgene activation Genes & development High 20971813
2014 STAG3 stabilizes REC8 cohesin complexes during meiosis. In hypomorphic Stag3 mice with severely reduced STAG3, REC8 cohesin levels are reduced and meiocytes display chromosome axis compaction defects, aberrant synapsis, and impaired recombination. STAG3-REC8 cohesin complexes have a critical role in meiotic chromosome structure and function. Hypomorphic Stag3 mouse model, immunofluorescence, analysis of cohesin subunit dosage and meiotic phenotypes The EMBO journal High 24797475
2016 Cohesin established by Rec8 in fetal mouse oocytes is maintained without detectable turnover in oocytes arrested for months (dictyate stage). Rec8 activated during DNA replication in fetal oocytes establishes cohesion, but Rec8 activated in already-arrested oocytes does not establish new cohesion despite cohesin synthesis, demonstrating that cohesion establishment requires ongoing DNA replication. Tamoxifen-inducible Cre activation of Rec8 transgene in fetal vs. arrested oocytes, TEV cleavage assay, live-cell imaging Current biology : CB High 26898469
2016 High density of REC8 cohesin complexes along chromosome axes is required to constrain sister chromatid axes and prevent illegitimate inter-sister synaptonemal complex formation. Using super-resolution microscopy, REC8 foci are separated by <15% of total axis length in wild-type meiocytes; reduced cohesin levels lead to local axial separation and ectopic SC formation specifically at REC8-free sites. Super-resolution microscopy (STED/SIM) in hypomorphic Stag3 mouse meiocytes with reduced REC8 levels EMBO reports Medium 27170622
2016 During meiotic prophase, Rec8 phosphorylation by Dbf4-dependent Cdc7 kinase (DDK) promotes crossover-specific events independently of cohesin cleavage. Rec8 phospho-mutants (with 6, 24, or 29 alanine substitutions) show normal axis formation and recombination initiation but defective crossover formation, with severity proportional to number of substitutions. Inhibition of DDK (but not Hrr25/CK1 or Cdc5/PLK) during prophase recapitulates rec8 phospho-mutant phenotypes. Rec8 phospho-alanine mutants, timed kinase inhibition, crossover and non-crossover recombination analysis in S. cerevisiae Nucleic acids research Medium 27484478
2016 RAD21L and REC8 meiotic cohesin subunits occupy distinct positions within the synaptonemal complex as determined by 3D-SIM super-resolution microscopy: both localize at connection sites between lateral elements and transverse filaments of pachynema, with RAD21L positioned interior to REC8 sites. RAD21L (but not REC8) forms bridges between unsynapsed axial elements at zygonema and shows greater overlap with recombination intermediates. 3D-SIM super-resolution microscopy of spermatocyte synaptonemal complexes The Journal of reproduction and development Medium 27665783
2016 The separase-cleaved C-terminal fragment of mammalian Rec8 bears N-terminal Glu, which is arginylated by Ate1 R-transferase and then degraded by the N-end rule pathway. Male germ cell-specific Ate1 knockout mice are nearly infertile due to massive apoptotic death of spermatocytes at metaphase I, caused by failure to destroy the C-terminal Rec8 fragment. Germ cell-specific Ate1 knockout mouse, biochemical analysis of Rec8 fragments, in vivo protein stability assays The Journal of biological chemistry High 26858254
2018 When expressed in somatic (Hek293) cells, Rec8 has no affinity for Stag1 or Stag2 and remains cytoplasmic, but co-expression of Stag3 is sufficient for Rec8 to enter the nucleus, load onto chromatin, and replace Scc1 for sister chromatid cohesion. Rec8-Stag3 cohesin physically interacts with Pds5, Wapl, and sororin, and is susceptible to Wapl-dependent ring opening and sororin-mediated protection. Ectopic expression in Hek293 cells, chromatin fractionation, co-immunoprecipitation, sister chromatid cohesion assays Journal of cell science High 29724914
2018 Meiosis-specific cohesin component Rec8 binds to Mps3 SUN domain 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, requiring the cohesin regulator Rad61/Wpl1 (WAPL). Co-immunoprecipitation, ectopic Rec8 expression in mitotic yeast, fluorescence microscopy of nuclear envelope localization in S. cerevisiae Genes to cells : devoted to molecular & cellular mechanisms Medium 30417519
2020 EWSR1 binds to both PRDM9 and phosphorylated REC8 (pREC8) in male meiotic cells. Conditional knockout of Ewsr1 before meiosis onset causes meiotic arrest with decreased H3K4/K36 trimethylation at hotspots, impaired DSB repair, and reduced crossover number, suggesting EWSR1 links PRDM9-bound hotspots to the chromosome axis through pREC8. Co-immunoprecipitation of EWSR1 with PRDM9 and pREC8, conditional Ewsr1 knockout mouse, ChIP-seq for histone methylation Molecular biology of the cell Medium 33175657
2021 Cleavage of pericentromeric REC8 by Separase at meiosis I is necessary not only for converting sister kinetochores from co-orientation to bi-orientation at meiosis II but also for deprotection of pericentromeric cohesion. Selective cleavage of REC8 in the vicinity of kinetochores in univalent chromosomes is sufficient to destroy co-orientation. This was demonstrated by transferring spindle-chromosome complexes between meiosis I and II in mouse oocytes. Spindle-chromosome complex transfers between meiosis I and II oocytes, TEV cleavage of REC8, live imaging in mouse oocytes Developmental cell High 34758289
2021 Overexpression of Rec8 (or Spo11) in proliferating fission yeast and human cells leads to the loss of mitotic kinetochores, demonstrating that Rec8 can dismantle centromeric chromatin. Specific nucleosome remodeling factors mediate centromere dismantlement by Rec8. This centromere dismantlement is normally observable only in mutants lacking the telomere bouquet. Overexpression of Rec8 in fission yeast and human cells, kinetochore loss assays, identification of mediating nucleosome remodeling factors Nature Medium 33658710
2021 Meikin (Moa1 in fission yeast) associates with Plo1 kinase and phosphorylates Rec8, with a key phosphorylation site required for cohesion protection. The phosphorylation of Rec8 by Moa1-Plo1 potentiates PP2A activity associated with Sgo1, leading to dephosphorylation of Rec8 at another site, thereby preventing separase cleavage of centromeric Rec8. Genetic analysis, phosphorylation site mapping, epistasis between moa1, plo1, sgo1 and rec8 phospho-mutants in S. pombe Genes & development High 33888556
2022 Aurora B/C kinase activities promote REC8 phosphorylation and cleavage in mammalian oocytes. Through phosphomutant analysis using a separase biosensor in live mouse oocytes, specific phosphorylation sites in Rec8 that promote its cleavage were identified. Inhibition of Aurora B/C during meiotic maturation impairs endogenous Rec8 phosphorylation and chromosome segregation. Fluorescent biosensor for Rec8 cleavage, microinjection into mouse oocytes, phosphomutant analysis, Aurora B/C inhibitor treatment, live imaging Current biology : CB High 35385691
2022 MicroRNA-202 (miR-202) represses Separase mRNA, thereby upregulating REC8 protein levels. Loss of miR-202 results in premature SEPARASE-mediated REC8 cleavage, spermatocyte apoptosis, and disrupted meiotic prophase I (synapsis and crossover defects, inter-sister chromatid synapses). Separase mRNA is a direct target of miR-202. miR-202 knockout mice, luciferase reporter assays demonstrating Separase as direct miR-202 target, immunofluorescence of REC8 and synapsis markers EMBO reports Medium 35712867
2023 Cleavage-independent dissociation of Rec8 cohesin from chromosomes occurs during meiotic prophase I in response to DSBs. Genome-wide Rec8 binding profiles change from mid- to late-prophase I, and the ratio of Rec8 dissociation per chromosome correlates with meiotic DSB density. In the spo11 mutant deficient in DSB formation, Rec8 distribution does not change in late prophase I, demonstrating a DSB-dependent regulatory pathway for global Rec8-cohesin binding. Genome-wide ChIP-seq of Rec8 at mid- and late-prophase I, spo11 mutant analysis in S. cerevisiae Genes to cells : devoted to molecular & cellular mechanisms Medium 37968127
2024 Plo1 (polo-like kinase) associated with meikin (Moa1) phosphorylates Rec8 at specific sites to regulate sister kinetochore mono-orientation at meiosis I. Non-phosphorylatable mutations at these Plo1 phosphorylation sites in Rec8 (and Psm3) cause specific mono-orientation defects without affecting cohesion protection, enabling genetic dissection of these two meikin functions. Identification of Plo1 phosphorylation sites in Rec8 and Psm3, non-phosphorylatable mutant analysis, kinetochore orientation assays in S. pombe Life science alliance Medium 38448160
2024 Acetyltransferase Eso1 acetylates meiosis-specific Rec8 cohesin complexes at a new site, Psm3-K1013, which is largely dependent on the meiotic kinetochore factor meikin (Moa1). This acetylation cooperates with canonical Psm3-K105/K106 acetylation and plays a crucial role in establishing reductional chromosome segregation in meiosis. Purification of centromeric Rec8 cohesin complexes from meiotic cells, mass spectrometry identification of acetylation site, genetic analysis of Psm3-K1013 mutants in S. pombe Life science alliance Medium 38575358
2022 In S. pombe, Sgo1 and Moa1 are degraded during anaphase I by the APC/C-Slp1 pathway. Non-degradable Sgo1 and Moa1 expressed in meiosis II can protect Rec8 cohesin. Sgo1 localization and phosphorylation of Rec8 at S449 and S450 are necessary and sufficient events for protecting Rec8 cohesin, with absence of either event leading to Rec8 deprotection at meiosis II. Non-degradable Sgo1/Moa1 mutant expression in meiosis II, phosphomutant analysis of Rec8 S449/S450, live imaging in S. pombe bioRxivpreprint Medium
2025 REC8-cohesin preferentially localizes to open promoter regions of genes involved in spermatogonial differentiation and meiosis at early meiosis (preleptonema to zygonema). REC8-cohesin genomic distribution is altered by BEND2 knockout. REC8 interacts with mitotic cyclin CCNA2. These findings demonstrate that REC8-cohesin participates in chromatin reorganization and transcription regulation at the mitosis-to-meiosis transition. ChIP-seq for REC8, BEND2 KO mice, co-immunoprecipitation of REC8 with CCNA2, RNA-seq Genomics, proteomics & bioinformatics Medium 41476252
2022 REC8 interacts with MAVS and STING in the cytoplasm and inhibits their K48-linked ubiquitination triggered by RNF5, stabilizing these innate immune signaling proteins. SUMOylated REC8 translocates from nucleus to cytoplasm during viral infection and promotes recruitment of TBK1 to MAVS and STING. Knockdown of REC8 impairs innate immune responses against VSV, NDV, and HSV. Co-immunoprecipitation of REC8 with MAVS and STING, ubiquitination assays, REC8 knockdown with viral infection assays, REC8 SUMOylation and localization analysis Journal of virology Medium 35107381

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Cohesin Rec8 is required for reductional chromosome segregation at meiosis. Nature 449 10440376
2005 Absence of mouse REC8 cohesin promotes synapsis of sister chromatids in meiosis. Developmental cell 266 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 173 8536990
2010 Rec8 phosphorylation by casein kinase 1 and Cdc7-Dbf4 kinase regulates cohesin cleavage by separase during meiosis. Developmental cell 152 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 134 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 114 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
2014 STAG3-mediated stabilization of REC8 cohesin complexes promotes chromosome synapsis during meiosis. The EMBO journal 85 24797475
2009 Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. Journal of cell science 85 19625504
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 56 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
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
2016 Genetic Interactions Between the Meiosis-Specific Cohesin Components, STAG3, REC8, and RAD21L. G3 (Bethesda, Md.) 47 27172213
2016 REC8 functions as a tumor suppressor and is epigenetically downregulated in gastric cancer, especially in EBV-positive subtype. Oncogene 41 27212034
2021 Meiotic genes in premature ovarian insufficiency: variants in HROB and REC8 as likely genetic causes. European journal of human genetics : EJHG 39 34707299
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
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
2021 Interplay between Pds5 and Rec8 in regulating chromosome axis length and crossover frequency. Science advances 28 33712462
2022 Rec8 Cohesin: A Structural Platform for Shaping the Meiotic Chromosomes. Genes 27 35205245
2021 Loss of sister kinetochore co-orientation and peri-centromeric cohesin protection after meiosis I depends on cleavage of centromeric REC8. Developmental cell 27 34758289
2018 REC8 inhibits EMT by downregulating EGR1 in gastric cancer cells. Oncology reports 27 29393474
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 24 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
2022 MicroRNA-202 safeguards meiotic progression by preventing premature SEPARASE-mediated REC8 cleavage. EMBO reports 18 35712867
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
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
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
2018 Cloning and characterization of the homoeologous genes for the Rec8-like meiotic cohesin in polyploid wheat. BMC plant biology 9 30305022
2022 Disruption of REC8 in Meiosis I led to watermelon seedless. Plant science : an international journal of experimental plant biology 8 35905897
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 4 38448160
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 4 35951744
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
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
2022 Protocol to measure cleavage efficiency of the meiotic cohesin subunit Rec8 by separase in mouse oocytes using a biosensor. STAR protocols 1 36149797
2026 The dynamic pool of Rec8-cohesin is crucial for meiotic recombination and transcription regulation in the yeast Saccharomyces 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

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