Affinage

BRME1

Break repair meiotic recombinase recruitment factor 1 · UniProt Q0VDD7

Length
668 aa
Mass
69.6 kDa
Annotated
2026-06-09
14 papers in source corpus 8 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BRME1 (C19orf57/MEIOK21) is a meiosis-specific protein that promotes homologous recombination at meiotic DNA double-strand breaks (DSBs) by organizing a BRCA2-MEILB2(HSF2BP) recombinase-loading complex (PMID:32460033, PMID:32345962). It binds the α-helical N-terminus of MEILB2 and prevents MEILB2 self-association, thereby stabilizing MEILB2 and the BRCA2-MEILB2 complex; BRCA2 engages the MEILB2 C-terminus to assemble a BRCA2-MEILB2-BRME1 ternary complex (PMID:32345962). Structurally, MEILB2-BRME1 forms a parallel four-helical 2:2 core carrying an N-terminal β-cap that binds DNA, and upon BRCA2 binding these cores dimerize into a V-shaped 2:4:4 DNA clamp whose two β-caps are separated by ~25 nm, allowing it to bridge between DNA molecules or homologous chromosomes (PMID:39095423). BRME1 also acts as a regulatory switch on MEILB2 oligomerization: it dissociates the octameric and BRCA2-induced 24-mer rings formed by MEILB2 and protects BRCA2 from degradation during interstrand crosslink repair (PMID:37889963). On meiotic chromosomes BRME1 localizes in a DSB-dependent manner, progressing through on-axis foci, hanging foci, bridges, and fused foci, and its loss reduces MEILB2, RAD51, and DMC1 foci, impairing DSB repair, synapsis, and crossover formation and causing male infertility (PMID:32845237, PMID:32463460). Ectopic somatic expression of the MEILB2-BRME1 complex disrupts mitotic homologous recombination, linking misregulation of this meiotic module to cancer (PMID:32345962).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2020 High

    Established that BRME1 is a meiotic component of the BRCA2-MEILB2 recombinase-loading machinery, answering whether a then-uncharacterized protein contributes to RAD51/DMC1 loading at meiotic DSBs.

    Evidence Co-IP of BRME1 with BRCA2 and MEILB2 plus knockout mouse cytology of DSB repair foci

    PMID:32460033

    Open questions at the time
    • Did not resolve the structural basis of complex assembly
    • Mechanism of how recombinase loading is delayed not defined at molecular level
  2. 2020 High

    Defined BRME1's molecular role as a MEILB2 stabilizer that binds the MEILB2 N-terminus and blocks self-association, building a defined BRCA2-MEILB2-BRME1 ternary complex and explaining why BRME1 loss destabilizes the complex.

    Evidence Co-IP with binding-domain mapping and knockout mouse with synapsis/crossover readouts

    PMID:32345962

    Open questions at the time
    • Atomic structure of the complex not yet determined
    • Stoichiometry of the ternary complex unresolved
  3. 2020 High

    Independently confirmed the BRME1-MEILB2 interaction and connected it to a hypomorphic HSF2BP variant, showing the complex co-purifies with BRCA2, RAD51, RPA, and PALB2 and is required for recombination nodule localization.

    Evidence Co-IP of multiple complex members plus knock-in/knockout mouse immunofluorescence cytology

    PMID:32845237

    Open questions at the time
    • Direct versus indirect nature of RPA/PALB2 association not distinguished
    • Order of recruitment to recombination nodules unclear
  4. 2020 High

    Characterized BRME1's dynamic, DSB-dependent chromosomal localization through on-axis foci, hanging foci, bridges, and fused foci, framing it as a structural component of meiotic recombination bridges between homolog axes.

    Evidence Knockout mouse with detailed immunofluorescence cytology and physical interaction assays

    PMID:32463460

    Open questions at the time
    • Molecular trigger for the focus-to-bridge transition not defined
    • How bridges physically tether homologs not shown structurally
  5. 2020 Medium

    Tested whether the meiotic complex is pathogenic when misexpressed somatically, showing ectopic MEILB2-BRME1 impairs mitotic homologous recombination and is activated in cancers.

    Evidence Ectopic expression in cancer cell lines with HR functional assay

    PMID:32345962

    Open questions at the time
    • Single lab, no independent replication
    • Mechanism of HR impairment in somatic cells not dissected
  6. 2023 High

    Revealed that BRME1 acts as a switch over MEILB2 oligomeric state, dissociating MEILB2 octamer and BRCA2-induced 24-mer rings and protecting BRCA2 from degradation during crosslink repair.

    Evidence EM of oligomeric rings, Xenopus egg extract crosslink-repair assay, and cancer-cell DNA-damage resistance assay

    PMID:37889963

    Open questions at the time
    • Physiological relevance of ring assembly in meiosis not established
    • Single lab
  7. 2024 High

    Resolved the structural architecture of the complex, showing a parallel four-helical 2:2 MEILB2-BRME1 core with a DNA-binding β-cap that, upon BRCA2 binding, forms a V-shaped 2:4:4 DNA clamp able to bridge DNA molecules or chromosomes.

    Evidence X-ray crystallography with in vitro DNA-binding assays and in vivo recruitment studies

    PMID:39095423

    Open questions at the time
    • DNA bridging not directly visualized on chromosomes
    • How the clamp interfaces with RAD51/DMC1 loading not resolved
  8. 2024 Medium

    Identified epigenetic control of BRME1 expression, showing the PRC1.6 component L3MBTL2 silences BRME1 via H2AK119ub and that this axis supports neuroblastoma proliferation.

    Evidence L3MBTL2 knockout/knockdown in neuroblastoma cells, ChIP for H2AK119ub, transcriptomics, and add-back

    PMID:39189159

    Open questions at the time
    • Direct role of BRME1 protein in proliferation is indirect
    • Single lab; mechanism downstream of BRME1 de-repression unclear
  9. 2026 Medium

    Showed post-transcriptional control of Brme1 mRNA, with PCBP2 recruiting hnRNPU and DDX5 to regulate its stability and splicing in spermatocytes.

    Evidence IP-MS, RNA-Seq, RIP-Seq in Pcbp2 germline knockout mice

    PMID:41655928

    Open questions at the time
    • BRME1 is one of several PCBP2 targets; specific contribution to phenotype not isolated
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the BRME1-MEILB2-BRCA2 DNA clamp mechanically couples chromosome bridging to RAD51/DMC1 nucleofilament assembly at meiotic DSBs remains undefined.
  • No direct visualization of recombinase handoff from the clamp
  • Regulation distinguishing meiotic from aberrant somatic activity not mechanistically resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0140313 molecular sequestering activity 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-1474165 Reproduction 2 R-HSA-73894 DNA Repair 2
Partners
BRCA2HSF2BP
Complex memberships
BRCA2-MEILB2(HSF2BP)-BRME1 ternary complex

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 BRME1 (C19orf57/4930432K21Rik) associates with the ssDNA binding proteins BRCA2 and MEILB2/HSF2BP, forming a complex critical for loading recombinases onto DSB sites. In Brme1 KO spermatocytes, removal of ssDNA binding proteins from DSB sites is delayed and loading of RAD51 and DMC1 onto resected ssDNA is impaired. Co-immunoprecipitation, knockout mouse model with cytological analysis of DSB repair foci Cell Reports High 32460033
2020 BRME1 functions as a stabilizer of MEILB2 by binding to the α-helical N-terminus of MEILB2 and preventing MEILB2 self-association. BRCA2 binds to the C-terminus of MEILB2, resulting in formation of a BRCA2-MEILB2-BRME1 ternary complex. In Brme1-/- mice, the BRCA2-MEILB2 complex is destabilized, leading to defects in DSB repair, homolog synapsis, and crossover formation. Co-immunoprecipitation, knockout mouse model, structural/biochemical binding domain mapping Nature Communications High 32345962
2020 BRME1 is a strong interactor and stabilizer of HSF2BP (MEILB2), and the BRME1/HSF2BP complex co-immunoprecipitates with BRCA2, RAD51, RPA, and PALB2. A hypomorphic HSF2BP-S167L variant causes strongly decreased staining of both HSF2BP and BRME1 at recombination nodules and reduced RAD51/DMC1 foci, leading to fewer crossovers. Co-immunoprecipitation, mouse genetics (knock-in and knockout), immunofluorescence cytology eLife High 32845237
2020 MEIOK21 (BRME1) is a component of meiotic recombination bridges that dynamically localizes on chromosomes from on-axis foci to 'hanging foci', then to 'bridges', and finally to 'fused foci' between homolog axes. Its chromosome localization depends on DSBs. Knockout decreases HSF2BP and DMC1/RAD51 foci numbers, disrupting DSB repair, synapsis, and crossover recombination, causing male infertility. BRME1 physically interacts with HSF2BP. Knockout mouse model, immunofluorescence cytology, physical interaction assay (co-immunoprecipitation/pulldown) Nucleic Acids Research High 32463460
2020 MEILB2-BRME1 is activated/expressed in many human cancers, and somatically expressed MEILB2-BRME1 impairs mitotic homologous recombination, implicating misregulation of this meiotic complex in cancer development. Ectopic expression in somatic/cancer cell lines, HR functional assay Nature Communications Medium 32345962
2024 Crystal structure of the MEILB2-BRME1 2:2 core complex reveals a parallel four-helical assembly with an N-terminal β-cap that binds DNA and a MEILB2 coiled-coil bridging to C-terminal ARM domains. Upon BRCA2 binding, MEILB2-BRME1 2:2 complexes dimerize into a V-shaped 2:4:4 complex with β-caps separated by 25 nm, forming a DNA clamp that can bridge between DNA molecules or homologous chromosomes. X-ray crystallography, in vitro biochemical assays, in vivo localization studies Nature Communications High 39095423
2023 HSF2BP (MEILB2) forms octameric rings that interlock into a large ring-shaped 24-mer upon binding to BRCA2. Addition of BRME1 leads to dissociation of both ring structures, cancels the disruptive effect of HSF2BP on cancer cell resistance to DNA damage, and prevents BRCA2 degradation during interstrand DNA crosslink repair in Xenopus egg extracts. Structural biochemistry (electron microscopy of oligomeric rings), Xenopus egg extract assay, cancer cell DNA damage resistance assay Science Advances High 37889963
2024 L3MBTL2 (a PRC1.6 component) silences BRME1 in neuroblastoma cells via H2AK119ub histone modification at the BRME1 transcriptional start site. L3MBTL2 knockout de-represses BRME1 expression, and add-back studies show the L3MBTL2-BRME1 axis is important for neuroblastoma cell proliferation. Knockout and knockdown of L3MBTL2 in neuroblastoma cells, ChIP for H2AK119ub, transcriptome analysis, add-back experiments Genes to Cells Medium 39189159
2026 PCBP2 recruits hnRNPU and DDX5 to Brme1 mRNA to regulate its stability and alternative splicing in spermatocytes. PCBP2 germline knockout reduces BRME1 transcript processing, contributing to delayed meiotic prophase. IP-MS, RNA-Seq, RIP-Seq in Pcbp2 germline knockout mice International Journal of Biological Macromolecules Medium 41655928

Source papers

Stage 0 corpus · 14 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination. Cell reports 49 32460033
2020 The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells. Nature communications 42 32345962
2020 A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1. eLife 32 32845237
2019 Transcriptome sequencing profiles of cervical cancer tissues and SiHa cells. Functional & integrative genomics 31 31456134
2020 MEIOK21: a new component of meiotic recombination bridges required for spermatogenesis. Nucleic acids research 25 32463460
2023 Liver transcriptome profiles of dairy cows with different serum metabotypes. Journal of dairy science 9 37806621
2021 BRCA2 in mammalian meiosis. Trends in cell biology 6 34625364
2023 Alternative splicing event associated with immunological features in bladder cancer. Frontiers in oncology 5 36686818
2023 Therapeutic implications of transcriptomics in head and neck cancer patient-derived xenografts. PloS one 5 36857322
2024 L3MBTL2 maintains MYCN-amplified neuroblastoma cell proliferation through silencing NRIP3 and BRME1 genes. Genes to cells : devoted to molecular & cellular mechanisms 4 39189159
2024 MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination. Nature communications 3 39095423
2023 BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination. Science advances 2 37889963
2026 The Poly(rC) binding protein 2 is required for spermatogenesis by regulating alternative splicing and mRNA stability. International journal of biological macromolecules 0 41655928
2021 [Peripheral blood EMR3 gene methylation level is correlated with breast cancer in Chinese women]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 34755660

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