Affinage

REC114

Meiotic recombination protein REC114 · UniProt Q7Z4M0

Length
266 aa
Mass
29.2 kDa
Annotated
2026-04-28
19 papers in source corpus 16 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

REC114 is a meiosis-specific factor essential for the initiation of programmed DNA double-strand breaks (DSBs) that drive meiotic recombination. It forms a conserved 2:1 heterotrimer with MEI4, where two REC114 C-terminal domains cup an MEI4 N-terminal α-helix; this complex preferentially binds branched DNA and drives DNA condensation through multivalent bridging interactions (PMID:37442581, PMID:37442580, PMID:30569039). The REC114 N-terminal PH domain serves as a regulatory hub mediating mutually exclusive interactions with IHO1/Mer2 (linking the complex to chromosome axes), ANKRD31 (directing DSBs to specific loci including pseudoautosomal regions), and TOPOVIBL (coupling the axis machinery to the SPO11 catalytic complex), while ATM/ATR-dependent phosphorylation of REC114 displaces it from hotspot chromatin to enforce DSB homeostasis (PMID:37431931, PMID:36396648, PMID:31003867, PMID:23825959). Biallelic loss-of-function mutations in human REC114 cause meiotic arrest manifesting as nonobstructive azoospermia or female infertility with multiple pronuclei and early embryonic arrest (PMID:38148155, PMID:31704776).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1993 Medium

    Establishing that REC114 is a meiosis-specific gene required for recombination initiation answered whether REC114 functions exclusively in meiosis and placed it in the DSB-formation pathway.

    Evidence Null mutant characterization and Northern blot in budding yeast

    PMID:8385581

    Open questions at the time
    • Molecular mechanism of how REC114 promotes DSBs unknown
    • Physical interaction partners not identified
    • No structural information available
  2. 2006 High

    Demonstrating that Rec114 forms a physical complex with Mer2 and Mei4 that co-localizes on meiotic chromosomes established a distinct protein subcomplex within the DSB machinery.

    Evidence Reciprocal co-immunoprecipitation and immunofluorescence co-localization in yeast

    PMID:16783010

    Open questions at the time
    • Stoichiometry and architecture of the Rec114-Mei4-Mer2 complex unknown
    • How this complex connects to the Spo11 catalytic core not defined
  3. 2007 Medium

    Defining Rec114-Mei4-Mer2 as a functional subgroup separate from Spo11-Ski8 and identifying Rec102/Rec104 as connectors clarified the modular architecture of the DSB machinery and how Rec114 influences Spo11 self-association.

    Evidence Two-hybrid interaction mapping, genetic epistasis, and co-IP of differentially tagged Spo11 in yeast

    PMID:17264124 PMID:17558514

    Open questions at the time
    • Direct structural basis of Rec114's contribution to Spo11 activity not resolved
    • Chromosome-loop versus axis association of Rec114 debated
  4. 2013 High

    Showing that ATM/ATR phosphorylate Rec114 to reduce its association with DSB hotspot DNA revealed a negative-feedback mechanism enforcing DSB homeostasis, answering how cells limit DSB numbers.

    Evidence Phosphomimetic/non-phosphorylatable mutants with ChIP and genome-wide DSB quantification in yeast

    PMID:23825959

    Open questions at the time
    • Precise phosphosites mediating chromatin dissociation not fully mapped
    • Whether phosphorylation-dependent regulation is conserved in mammals untested at this stage
    • Ndt80-dependent degradation mechanism not biochemically defined
  5. 2018 High

    Demonstrating that mouse REC114 is essential for meiotic DSBs, forms a complex with MEI4 and IHO1, and possesses an N-terminal PH domain established evolutionary conservation and provided the first structural framework for REC114.

    Evidence Mouse knockout, in vitro reconstitution of REC114-MEI4 complex, crystal structure

    PMID:30569039

    Open questions at the time
    • PH domain binding partners not yet identified
    • Stoichiometry of the REC114-MEI4 complex not resolved
    • How IHO1 connects the complex to the axis not structurally defined
  6. 2019 High

    Solving the crystal structure of the REC114 PH domain bound to ANKRD31 and showing ANKRD31 directs DSBs to the pseudoautosomal region via REC114 established the PH domain as a protein-interaction platform that controls DSB targeting.

    Evidence Crystal structure, mouse knockout of ANKRD31, co-IP, cytological analysis

    PMID:31003867

    Open questions at the time
    • Whether additional partners engage the same PH domain surface unknown
    • Mechanism by which ANKRD31-REC114 interaction specifies PAR targeting not fully resolved
  7. 2022 High

    Identifying REC114 as a direct binding partner of TOPOVIBL and showing that disruption of this interaction impairs DSB activity answered how the axis-associated REC114 complex communicates with the SPO11 catalytic machinery.

    Evidence Structural analysis of REC114-TOPOVIBL domains, point mutagenesis with in vivo DSB monitoring in mouse mutants

    PMID:36396648

    Open questions at the time
    • Full reconstitution of the complete SPO11-TOPOVIBL-REC114 assembly not achieved
    • Whether REC114-TOPOVIBL interaction is regulated by phosphorylation unknown
  8. 2023 High

    Resolving the 2:1 REC114-MEI4 heterotrimer architecture and demonstrating that IHO1, TOPOVIBL, and ANKRD31 compete for the same PH domain surface established REC114 as a regulatory switch coordinating axis association, DSB catalysis, and locus targeting through mutually exclusive interactions.

    Evidence AlphaFold2 modeling validated by SEC, co-IP, and biochemical reconstitution; NMR and SAXS of the heterotrimer; single-molecule DNA condensation assays; mouse point-mutant genetics for ANKRD31-REC114 interface

    PMID:37431931 PMID:37442580 PMID:37442581 PMID:37976262

    Open questions at the time
    • How switching between PH-domain partners is temporally regulated in vivo is unknown
    • Whether DNA condensation by REC114-MEI4 is required for DSB formation in vivo untested
    • Full reconstitution of RMM condensates with SPO11 catalytic activity not achieved
  9. 2023 Medium

    Human genetic studies confirmed that loss-of-function REC114 mutations cause meiotic arrest, linking the REC114-MEI4 axis to nonobstructive azoospermia and female infertility with multiple pronuclei.

    Evidence Patient mutation analysis (p.Gln190*, p.C133G, splice-site variant), co-IP, histopathology

    PMID:31704776 PMID:38148155

    Open questions at the time
    • Genotype-phenotype correlations across a larger patient cohort not established
    • Functional rescue experiments in human germline cells not performed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include how the temporal switching between mutually exclusive PH-domain partners is regulated in vivo, whether REC114-MEI4-driven DNA condensation is mechanistically required for DSB catalysis, and whether mammalian REC114 phosphorylation enforces DSB homeostasis as in yeast.
  • No reconstitution of SPO11-catalyzed DSB formation with purified REC114-MEI4-IHO1 complex
  • In vivo relevance of DNA condensation activity not tested
  • Mammalian phospho-regulation of REC114 not directly demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0003677 DNA binding 2
Localization
GO:0005694 chromosome 3
Pathway
R-HSA-1474165 Reproduction 4
Partners
ANKRD31IHO1MEI4MER2SPO11TOPOVIBL
Complex memberships
REC114-MEI4 heterotrimerREC114-MEI4-IHO1/Mer2 (RMM) complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 REC114 is a meiosis-specific gene required for meiotic recombination initiation, transcribed only during meiosis in an IME1-dependent manner, with no detectable function in mitosis. Genetic analysis, Northern blot hybridization, null mutant characterization Current genetics Medium 8385581
1999 High copy numbers of REC114 suppress meiotic DSB formation, indicating that overexpression of REC114 blocks double-strand break recombination intermediates in yeast. High-copy suppressor screen, genetic epistasis in dmc1 mutant background Genes to cells Medium 10526232
2006 Mer2, Mei4, and Rec114 form a distinct protein complex required for meiotic DSB formation in budding yeast, as shown by co-immunoprecipitation and co-localization on meiotic chromosome foci. Co-immunoprecipitation, immunofluorescence co-localization on meiotic chromosomes Genetics High 16783010
2007 Rec114 localizes to meiotic chromosomes from leptonema through early pachynema, with localization independent of other DSB factors, and preferentially associates with chromatin loops rather than the meiotic cohesin Rec8. Immunofluorescence, chromosome spreads, genetic dependency analysis Chromosoma Medium 17558514
2007 Mei4, Rec114, and Mer2 form a functional subgroup distinct from other DSB protein subgroups (Spo11-Ski8, Rec102-Rec104, and Mre11-Rad50-Xrs2); Rec102 and Rec104 connect Mei4 and Rec114 to Spo11. Two-hybrid interaction analysis, systematic deletion analysis, genetic epistasis Chromosoma Medium 17558514
2007 Spo11 self-interaction during meiosis is genetically regulated by Rec102, Rec104, and Rec114, as these proteins are required for Spo11 self-association at DSB sites. Co-immunoprecipitation of differentially tagged Spo11 proteins, chromatin analysis Nucleic acids research Medium 17264124
2013 Tel1 (ATM) and Mec1 (ATR) phosphorylate Rec114 upon meiotic DSB formation, reducing Rec114 interaction with DSB hotspot DNA and down-regulating further DSB formation; non-phosphorylatable Rec114 causes genome-wide increase in DSBs. Phosphomimetic and non-phosphorylatable mutant alleles, chromatin immunoprecipitation, DSB quantification PLoS genetics High 23825959
2013 Ndt80, a meiosis-specific transcription factor, contributes to Rec114 degradation, providing a third independent mechanism for regulating Rec114 activity and DSB homeostasis. Genetic analysis in ndt80 mutant, protein level monitoring PLoS genetics Medium 23825959
2018 Mouse REC114 is essential for meiotic DSB formation; MEI4 forms a complex with REC114 and IHO1 in mouse spermatocytes; the REC114 C-terminal domain and MEI4 N-terminal domain form a stable complex in vitro; the REC114 N-terminal domain has structural similarity to Pleckstrin homology (PH) domains. Mouse KO, co-immunoprecipitation, in vitro reconstitution of REC114-MEI4 complex, crystal structure determination Life science alliance High 30569039
2019 ANKRD31 directly interacts with REC114 via a pleckstrin homology (PH) domain in REC114, as defined by a crystal structure; ANKRD31 stabilizes REC114 association with the pseudoautosomal region and controls DSB number, timing, and location. Crystal structure of REC114 PH domain with ANKRD31, mouse KO, co-immunoprecipitation, cytological analysis Molecular cell High 31003867
2019 A missense mutation (p.C133G) in REC114 reduces protein level and abolishes its function to protect MEI4 from degradation; a splice-site mutation affects alternative splicing of REC114; both cause multiple pronuclei formation and early embryonic arrest in human female infertility. Western blotting, co-immunoprecipitation, 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 TOPOVIL catalytic complex); their conserved interacting domains were identified by structural analysis; disruption of this interaction by point mutations in TOPOVIBL strongly reduces DSB activity genome-wide in oocytes and in sub-telomeric regions in spermatocytes. Structural analysis of REC114-TOPOVIBL interaction, point mutagenesis, meiotic DSB monitoring in mouse mutants Nature communications High 36396648
2023 Mouse REC114 forms homodimers and associates with MEI4 as a 2:1 heterotrimer that further dimerizes; IHO1 forms coiled-coil-based tetramers; IHO1 directly interacts with the PH domain of REC114 at the same surface recognized by TOPOVIBL and ANKRD31, suggesting REC114 acts as a regulatory platform mediating mutually exclusive interactions. AlphaFold2 modeling, biochemical characterization, size-exclusion chromatography, co-immunoprecipitation The EMBO journal High 37431931
2023 Rec114-Mei4 forms a 2:1 heterotrimeric complex where Rec114 C-terminus dimers cup an N-terminal Mei4 α-helix; this complex binds preferentially to branched DNA substrates via two DNA-binding sites that point in opposite directions and drives DNA condensation; the structure is conserved across eukaryotes. NMR spectroscopy, SAXS, mutagenesis, single-molecule experiments, AlphaFold2 modeling Genes & development High 37442580 37442581
2023 The minimal Rec114 C-terminus/Mei4 N-terminus heterotrimer is sufficient to bind DNA, bridge two or more DNA duplexes, and form large dynamic condensates; single-molecule experiments show the complex can condense DNA through long-range interactions. NMR, in vitro DNA binding assays, single-molecule experiments, condensate formation assays Genes & development High 37442580
2023 ANKRD31-REC114 interaction is essential for ANKRD31 function: complete loss of ANKRD31-REC114 interaction causes delayed DSB formation, defects in DSB repair, and failure to target DSBs to the pseudoautosomal regions; the severity of DSB defects correlates with the degree of disruption of this interaction. Mouse genetics with point mutations and truncations targeting ANKRD31-REC114 interface, DSB quantification, cytological analysis Proceedings of the National Academy of Sciences of the United States of America High 37976262
2023 A truncating variant (p.Gln190*) in REC114 impairs interaction with MEI4, causing meiotic arrest and nonobstructive azoospermia in humans, confirming the REC114-MEI4 complex is essential for meiotic DSB homeostasis. Co-immunoprecipitation, Western blot in vitro, testicular histopathology, meiotic chromosome spread analysis Clinical genetics Medium 38148155
2025 Mre11 condensates are recruited to meiotic DSB sites through interaction with Mer2 via a short α-helix in the Mre11 C-terminal IDR; Rec114-Mei4 and Mer2 (RMM) condensates organize the meiotic DSB machinery and are required for Mre11 recruitment. In vitro condensate assays, in vivo foci analysis, mutagenesis of Mre11-Mer2 interface, genetic complementation bioRxivpreprint Medium bio_10.1101_2025.07.08.663703

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 110 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 88 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 79 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 34 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 17 37442581
2023 Characterization of the REC114-MEI4-IHO1 complex regulating meiotic DNA double-strand break formation. The EMBO journal 16 37431931
2023 Structure and DNA-bridging activity of the essential Rec114-Mei4 trimer interface. Genes & development 12 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 11 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