Affinage

REC114

Meiotic recombination protein REC114 · UniProt Q7Z4M0

Length
266 aa
Mass
29.2 kDa
Annotated
2026-06-10
19 papers in source corpus 16 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

REC114 is an evolutionarily conserved, meiosis-specific protein that nucleates assembly of the machinery generating programmed double-strand breaks (DSBs) that initiate meiotic recombination (PMID:8385581, PMID:16783010). It forms a distinct chromosome-associated complex with MEI4 and Mer2/IHO1 that localizes to meiotic chromatin loops and is required for DSB formation (PMID:16783010, PMID:17558514); its C-terminal alpha-helical domain dimerizes and directly binds the MEI4 N-terminal helix to build a 2:1 REC114:MEI4 heterotrimer that further dimerizes, with REC114 stabilizing MEI4 against degradation (PMID:30569039, PMID:37431931, PMID:37442581). The REC114-MEI4 complex carries two oppositely oriented DNA-binding sites that preferentially engage branched DNA, bridge and condense multiple DNA duplexes, and form condensates that promote DSB-machinery assembly (PMID:37442581, PMID:37442580). The REC114 N-terminal PH-like domain acts as a regulatory platform whose single binding surface mediates mutually exclusive interactions with IHO1, ANKRD31, and TOPOVIBL (the SPO11 catalytic partner) (PMID:30569039, PMID:31003867, PMID:37431931); ANKRD31 binding controls DSB timing and targeting, including DSBs to the pseudoautosomal region, while TOPOVIBL binding couples REC114 to the SPO11/TOPOVIL catalytic complex to license break formation (PMID:31003867, PMID:36396648, PMID:37431931). DSB levels are held in homeostasis by negative feedback: Tel1/Mec1 (ATM/ATR) phosphorylation of REC114 reduces its association with DSB hotspot chromatin, and Ndt80 drives REC114 degradation late in meiosis (PMID:23825959). In humans, truncating and missense REC114 variants that impair MEI4 binding cause meiotic arrest and non-obstructive azoospermia, and additional REC114 mutations are associated with embryonic arrest, establishing the REC114-MEI4 complex as indispensable for human fertility (PMID:31704776, PMID:38148155).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1993 Medium

    Established REC114 as a meiosis-specific factor whose loss abolishes recombination initiation, defining it as a dedicated meiotic gene rather than a general recombination component.

    Evidence Northern blot of meiotic transcription and genetic null analysis in S. cerevisiae

    PMID:8385581

    Open questions at the time
    • No molecular function for the protein identified
    • Mechanism of action in DSB initiation unknown
  2. 1999 Medium

    Showed that REC114 dosage is rate-limiting, since over-expression suppresses DSB formation, hinting at a regulatory role in break control.

    Evidence High-copy suppressor screen with DSB intermediate readout in budding yeast

    PMID:10526232

    Open questions at the time
    • Molecular basis of dosage sensitivity unresolved
    • No biochemical partners identified yet
  3. 2006 High

    Defined REC114 as part of a discrete Mer2-Mei4-Rec114 complex distinct from the Spo11 nuclease module, placing it in a dedicated pre-DSB sub-assembly.

    Evidence Reciprocal Co-IP and chromosome co-localization in S. cerevisiae

    PMID:16783010

    Open questions at the time
    • Stoichiometry and direct vs indirect interactions not resolved
    • Connection to the Spo11 catalytic complex unclear
  4. 2007 Medium

    Localized REC114 to chromatin loops independently of other DSB factors and showed Mei4 chromosome loading depends on it, ordering the assembly pathway.

    Evidence Chromosome immunofluorescence with cohesin co-staining and deletion-dependency tests

    PMID:17558514

    Open questions at the time
    • Direct DNA/chromatin binding by REC114 not demonstrated
    • Mechanism of loop targeting unknown
  5. 2007 Medium

    Connected the Mei4-Rec114 subgroup to Spo11 self-interaction via Rec102-Rec104, linking the regulatory module to nuclease activation.

    Evidence Co-IP of tagged Spo11 and two-hybrid analysis with genetic dependence assays

    PMID:17264124

    Open questions at the time
    • Direct REC114-Spo11 contact not established
    • Bridging architecture inferred rather than reconstituted
  6. 2013 High

    Revealed a DSB homeostasis feedback loop in which Tel1/Mec1 phosphorylation of REC114 reduces hotspot association and Ndt80 drives its degradation, explaining how break levels are bounded.

    Evidence Phosphosite mutagenesis, hotspot ChIP, DSB quantification and ndt80 genetics in yeast

    PMID:23825959

    Open questions at the time
    • Phosphorylation effect on complex structure not defined
    • Degradation pathway/E3 ligase not identified
  7. 2018 High

    Demonstrated conservation in mammals, with mouse REC114 essential for DSBs, defined the direct C-terminal REC114–MEI4 interaction, and identified the N-terminal PH-like fold.

    Evidence Knockout mouse DSB cytology, Co-IP in spermatocytes, in vitro reconstitution and crystallography

    PMID:30569039

    Open questions at the time
    • Function of the PH-like domain not yet assigned
    • How the complex engages DNA undefined
  8. 2019 High

    Identified the REC114 PH domain as the docking site for ANKRD31, which directs DSB timing and pseudoautosomal-region targeting, giving the domain a defined regulatory function.

    Evidence Crystal structure of REC114 PH domain with ANKRD31 and knockout-mouse DSB mapping

    PMID:31003867

    Open questions at the time
    • Whether PH domain binds other partners at the same surface not yet known
    • Mechanism of PAR-specific targeting incomplete
  9. 2019 Medium

    Linked REC114 directly to human reproductive disease by showing variants that destabilize REC114 or fail to protect MEI4 cause embryonic arrest.

    Evidence IP, western blot and minigene splicing assays in HEK293T cells with patient variants

    PMID:31704776

    Open questions at the time
    • In vivo meiotic phenotype of variants not assessed
    • Causality at organismal level inferred from cell-based assays
  10. 2022 High

    Established REC114 as a direct regulatory partner of TOPOVIBL within the SPO11/TOPOVIL catalytic complex, coupling the assembly platform to the nuclease.

    Evidence Structural domain mapping and TOPOVIBL point-mutant mice with genome-wide DSB mapping

    PMID:36396648

    Open questions at the time
    • How TOPOVIBL binding triggers catalysis not resolved
    • Temporal order relative to ANKRD31/IHO1 binding unclear
  11. 2023 High

    Resolved the heterotrimer architecture and showed the REC114 PH-domain surface mediates mutually exclusive binding to IHO1, ANKRD31 and TOPOVIBL, recasting REC114 as a competitive regulatory hub.

    Evidence AlphaFold2 modeling validated by SEC, biochemistry and Co-IP

    PMID:37431931

    Open questions at the time
    • What controls partner exchange in vivo unknown
    • Temporal regulation of competing interactions not defined
  12. 2023 High

    Defined the structural basis of REC114-MEI4 DNA engagement, showing two oppositely oriented DNA-binding sites and preference for branched DNA that drive condensation.

    Evidence AlphaFold2, NMR, SAXS, mutagenesis and DNA-binding assays

    PMID:37442581

    Open questions at the time
    • In vivo relevance of branched-DNA preference not tested
    • Link between condensation and Spo11 activation incomplete
  13. 2023 High

    Demonstrated that a minimal REC114-MEI4 complex bridges and condenses DNA duplexes via long-range force, providing a biophysical mechanism for organizing DSB machinery.

    Evidence In vitro reconstitution with condensate and single-molecule force experiments

    PMID:37442580

    Open questions at the time
    • Physiological condensate composition not defined
    • How bridging promotes Spo11 cleavage unresolved
  14. 2023 High

    Showed genetically that the ANKRD31-REC114 interaction is required and dosage-sensitive for ANKRD31 scaffold function, validating the structural interface in vivo.

    Evidence Engineered Ankrd31 missense/truncation mice with DSB and crossover analysis

    PMID:37976262

    Open questions at the time
    • Stoichiometric basis of dosage sensitivity unresolved
    • Whether REC114 limits or enables ANKRD31 at distinct loci unclear
  15. 2023 Medium

    Confirmed in human males that a truncating REC114 variant disrupting MEI4 binding causes meiotic arrest and azoospermia, cementing the complex's role in human fertility.

    Evidence Co-IP, western blot, testicular histopathology and meiotic spreads from patients

    PMID:38148155

    Open questions at the time
    • Single-family genetic evidence
    • Quantitative effect on DSB numbers in patients not measured

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the competing PH-domain interactions, phosphorylation feedback, and condensate formation are temporally coordinated to license a precise number and distribution of DSBs remains unresolved.
  • No integrated in vivo timeline of partner exchange
  • Mechanistic link between condensation and Spo11 catalysis missing
  • Regulatory inputs governing DSB number not fully mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005694 chromosome 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-1474165 Reproduction 2 R-HSA-1640170 Cell Cycle 2
Partners
ANKRD31IHO1MEI4MER2REC102SPO11TOPOVIBL
Complex memberships
Mer2/IHO1-MEI4-REC114 pre-DSB complexREC114-MEI4 heterotrimerSPO11/TOPOVIL catalytic complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 REC114 is a meiosis-specific gene in S. cerevisiae transcribed only during meiosis, with expression dependent on the IME1 gene product, and contains a URS1 consensus sequence in its promoter; a null rec114 mutation abolishes meiotic recombination initiation with no detectable mitotic function. Northern blot hybridization, genetic null mutation analysis Current genetics Medium 8385581
1997 REC114 contains a functional intron at its 3' end with a non-consensus AAG splice site; the intron is not essential for expression or meiotic function (intronless copy complements null mutation), but is evolutionarily conserved. Minigene/intron analysis, genetic complementation Molecular & general genetics : MGG Medium 9267437
1999 High copy numbers of REC114 suppress meiotic DSB formation in budding yeast, indicating that over-expression of Rec114 prevents formation of DSB recombination intermediates. High-copy suppressor screen, genetic analysis of DSB intermediates Genes to cells : devoted to molecular & cellular mechanisms Medium 10526232
2006 Mer2, Mei4, and Rec114 form a distinct protein complex required for meiotic DSB formation in S. cerevisiae; all three proteins co-immunoprecipitate, localize to overlapping foci on meiotic chromosomes, and are distinct from the Spo11-Ski8 and Mre11-Rad50-Xrs2 sub-complexes. Co-immunoprecipitation, chromosome immunofluorescence/co-localization Genetics High 16783010
2007 Rec114 localizes to meiotic chromosomes (leptonema through early pachynema) independently of other DSB factors, preferentially associating with chromatin loops rather than the cohesin axis; Mei4 localization is strongly dependent on Rec114 and Mer2. Chromosome immunofluorescence, co-localization with Rec8 (cohesin), systematic deletion analysis Chromosoma Medium 17558514
2007 Rec102, Rec104, and Rec114 are required for Spo11 self-interaction (homodimerization) in vivo during meiosis, as assessed by chromatin-bound complexes at DSB sites; Rec102 interacts with Rec114 and Mei4, suggesting Rec102-Rec104 connect the Mei4-Rec114 subgroup to Spo11. Co-immunoprecipitation of differentially tagged Spo11 proteins, two-hybrid interaction analysis, genetic dependence assays Nucleic acids research Medium 17264124
2013 Tel1 (ATM) and Mec1 (ATR) phosphorylate Rec114 following Spo11-induced DSB formation; phosphomimetic rec114 mutations reduce Rec114 interaction with DSB hotspot DNA and reduce/delay DSB formation, while non-phosphorylatable rec114 alleles cause genome-wide increases in both DSB levels and Rec114-hotspot association, establishing a feedback mechanism for DSB homeostasis. Phosphorylation site mutagenesis, ChIP (chromatin immunoprecipitation) at DSB hotspots, DSB quantification, genetic analysis in tel1/mec1 mutants PLoS genetics High 23825959
2013 Ndt80, a meiosis-specific transcription factor, contributes to Rec114 degradation late in meiosis, providing a third independent mechanism for down-regulating Rec114 activity. Genetic analysis in ndt80 mutants, protein level assays PLoS genetics Medium 23825959
2018 Mouse REC114 is essential for meiotic DSB formation; MEI4 forms a stable complex with REC114 and IHO1 in mouse spermatocytes; the REC114 C-terminal domain directly binds the MEI4 N-terminal domain in vitro; the REC114 N-terminal domain has structural similarity to Pleckstrin Homology (PH) domains. Knockout mouse analysis (cytological assessment of DSBs), Co-immunoprecipitation, in vitro protein complex reconstitution, X-ray crystallography/structural determination Life science alliance High 30569039
2019 ANKRD31 directly binds REC114 via its PH domain (crystal structure defined); ANKRD31 stabilizes REC114 association with the pseudoautosomal region (PAR) and other genomic locations; loss of ANKRD31 alters DSB locations (especially fails to target DSBs to PAR), delays DSB timing, and dysregulates DSB numbers. Crystal structure of REC114 PH domain with ANKRD31, knockout mouse analysis, cytological DSB localization and quantification Molecular cell High 31003867
2019 A human REC114 missense mutation (p.C133G) reduces protein levels in vitro and causes loss of its function to protect its partner MEI4 from degradation; a splice-site mutation (c.546+5G>A) disrupts normal alternative splicing of REC114. Both result in multiple pronuclei formation and early embryonic arrest. Immunoprecipitation, western blotting, minigene splicing assay in HEK293T cells Journal of medical genetics Medium 31704776
2022 REC114 is a direct binding partner of TOPOVIBL (the SPO11 partner in the mammalian TOPOVIL catalytic complex); structural analysis identified conserved interacting domains between REC114 and TOPOVIBL; point mutations in TOPOVIBL that disrupt REC114 binding strongly reduce DSB activity genome-wide in oocytes and in sub-telomeric regions in spermatocytes, establishing REC114 as a key regulatory component of the TOPOVIL catalytic complex. Structural analysis of interacting domains, point mutant mouse models, genome-wide DSB mapping Nature communications High 36396648
2023 Mouse REC114 forms homodimers and associates with MEI4 as a 2:1 REC114:MEI4 heterotrimer that further dimerizes; IHO1 forms coiled-coil-based tetramers and directly interacts with the PH domain of REC114 at the same surface recognized by TOPOVIBL and ANKRD31, suggesting REC114 is a regulatory platform mediating mutually exclusive interactions. AlphaFold2 modeling, biochemical characterization, size-exclusion chromatography, Co-immunoprecipitation The EMBO journal High 37431931
2023 The Rec114 C-terminus forms alpha-helical dimers that cup the Mei4 N-terminal alpha-helix in a heterotrimeric complex; Rec114-Mei4 contains two DNA-binding sites pointing in opposite directions that drive DNA condensation; Rec114-Mei4 preferentially binds branched DNA substrates; these structural features are conserved across eukaryotes. AlphaFold2 modeling, NMR spectroscopy, SAXS, mutagenesis, DNA binding assays Genes & development High 37442581
2023 The minimal Rec114-Mei4 heterotrimeric complex (lacking Rec114 intrinsically disordered region) is sufficient to bind DNA and form condensates; single-molecule experiments show the complex bridges two or more DNA duplexes and generates force to condense DNA through long-range interactions. In vitro reconstitution of minimal complex, DNA binding assays, condensate formation assays, single-molecule force experiments Genes & development High 37442580
2023 The ANKRD31-REC114 interaction is essential for ANKRD31 function in meiosis; complete disruption of this interaction mimics Ankrd31 null phenotype (delayed DSBs, altered DSB locations, PAR targeting failure); ANKRD31 functions as a scaffold that requires REC114 binding for its activity, with a dosage-sensitive relationship. Targeted Ankrd31 missense and truncation mouse mutants, cytological DSB analysis, crossover mapping Proceedings of the National Academy of Sciences of the United States of America High 37976262
2023 A truncating human REC114 variant (p.Gln190*) causes meiotic arrest and non-obstructive azoospermia; the truncated REC114 protein has impaired interaction with MEI4, establishing that the REC114-MEI4 complex is indispensable for meiotic DSB homeostasis in human males. Co-immunoprecipitation, western blot, testicular histopathology, meiotic chromosome spread analysis Clinical genetics Medium 38148155

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Interactions between Mei4, Rec114, and other proteins required for meiotic DNA double-strand break formation in Saccharomyces cerevisiae. Chromosoma 111 17558514
2013 Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery. PLoS genetics 100 23825959
2006 Saccharomyces cerevisiae Mer2, Mei4 and Rec114 form a complex required for meiotic double-strand break formation. Genetics 92 16783010
2019 REC114 Partner ANKRD31 Controls Number, Timing, and Location of Meiotic DNA Breaks. Molecular cell 91 31003867
1999 High copy number suppression of the meiotic arrest caused by a dmc1 mutation: REC114 imposes an early recombination block and RAD54 promotes a DMC1-independent DSB repair pathway. Genes to cells : devoted to molecular & cellular mechanisms 81 10526232
2018 Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with MEI4. Life science alliance 80 30569039
2019 Homozygous mutations in REC114 cause female infertility characterised by multiple pronuclei formation and early embryonic arrest. Journal of medical genetics 55 31704776
2007 Meiotic association between Spo11 regulated by Rec102, Rec104 and Rec114. Nucleic acids research 48 17264124
2022 TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks. Nature communications 36 36396648
1993 Genetic and molecular analysis of REC114, an early meiotic recombination gene in yeast. Current genetics 27 8385581
1997 Examination of the intron in the meiosis-specific recombination gene REC114 in Saccharomyces. Molecular & general genetics : MGG 21 9267437
2023 Evolutionary conservation of the structure and function of meiotic Rec114-Mei4 and Mer2 complexes. Genes & development 19 37442581
2023 Characterization of the REC114-MEI4-IHO1 complex regulating meiotic DNA double-strand break formation. The EMBO journal 18 37431931
2023 Structure and DNA-bridging activity of the essential Rec114-Mei4 trimer interface. Genes & development 13 37442580
2023 Essential roles of the ANKRD31-REC114 interaction in meiotic recombination and mouse spermatogenesis. Proceedings of the National Academy of Sciences of the United States of America 13 37976262
2023 A bi-allelic REC114 loss-of-function variant causes meiotic arrest and nonobstructive azoospermia. Clinical genetics 7 38148155
2020 Genetic Interactions of Histone Modification Machinery Set1 and PAF1C with the Recombination Complex Rec114-Mer2-Mei4 in the Formation of Meiotic DNA Double-Strand Breaks. International journal of molecular sciences 6 32290544
2023 Essential roles of the ANKRD31-REC114 interaction in meiotic recombination and mouse spermatogenesis. bioRxiv : the preprint server for biology 1 37162821
2025 Compound heterozygous REC114 variants in dizygotic twins causes meiotic arrest and non-obstructive azoospermia. Basic and clinical andrology 0 41168699

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