Affinage

ELOF1

Transcription elongation factor 1 homolog · UniProt P60002

Length
83 aa
Mass
9.5 kDa
Annotated
2026-06-09
23 papers in source corpus 14 papers cited in narrative 14 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

ELOF1 is a constitutive component of the RNA polymerase II (RNAPII) elongation complex that acts at the interface of transcription and DNA repair (PMID:34108663, PMID:40436841). In transcription-coupled nucleotide excision repair (TC-NER), ELOF1 binds RNAPII near K1268 and functions as a specificity/adaptor factor that positions the CRL4CSA ubiquitin ligase for ubiquitylation of stalled RNAPII at K1268, a step required for downstream assembly of the repair machinery (PMID:34108663). Structurally, ELOF1 stably docks UVSSA and CRL4CSA onto arrested RNAPII to drive ligase neddylation and activation, and orders a TFIIS-like element in UVSSA that extends into the polymerase pore to block TFIIS-mediated reactivation of the arrested complex (PMID:38316879). Downstream of ubiquitylation, ELOF1 works together with UVSSA and STK19 to recruit and correctly position TFIIH, enabling XPD helicase-driven dissociation of lesion-stalled RNAPII and efficient repair and transcription recovery (PMID:34108662, PMID:39547228, PMID:39547229, PMID:41554717). Cell-free reconstitution established ELOF1 as an essential factor for error-free TC-NER alongside CSB, CRL4CSA, and UVSSA (PMID:39547228, PMID:39547229), and its yeast ortholog Elf1 promotes Rad26(CSB) engagement of lesion-arrested polymerase, indicating a conserved mechanism (PMID:38194460). Beyond repair, ELOF1 is a core component of the promoter-proximal paused RNAPII complex: it enhances DSIF/NELF-induced pausing and, within the RNAPII-DSIF-NELF-ELOF1 assembly, sterically counteracts TFIIF to stabilize pausing (PMID:42244727), while cooperating with IWS1 to stimulate elongation velocity in the activated complex (PMID:40835814). This pausing/elongation scaffolding role is physiologically deployed in B cells, where ELOF1 stabilizes paused RNAPII at antibody loci to provide a platform for AID-mediated transcription-coupled damage required for class switch recombination and somatic hypermutation (PMID:40049162, PMID:40049160). ELOF1 is required for mouse development, and its loss causes peri-gastrulation lethality together with altered mutually exclusive exon usage (PMID:31276560).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2019 Medium

    Established that ELOF1 is essential in a mammalian organism and hinted at a transcription-linked function distinct from the yeast ortholog, framing it as more than a passive elongation factor.

    Evidence Mouse loss-of-function allele with phenotypic and splice-variant analysis

    PMID:31276560

    Open questions at the time
    • Mechanism linking ELOF1 to exon choice not resolved
    • No molecular partners identified
    • Single lab, limited mechanistic resolution
  2. 2020 Medium

    Placed ELOF1 in the cellular response to transcription-blocking lesions by showing its loss alters sensitivity to genotoxic agents, before any repair mechanism was defined.

    Evidence CRISPR-Cas9 chemogenetic screen in RPE1 cells

    PMID:32649862

    Open questions at the time
    • Phenotype only, no direct mechanistic role for ELOF1
    • Does not distinguish transcription vs repair function
  3. 2021 High

    Defined ELOF1 as the specificity factor that couples damage-stalled RNAPII to its ubiquitylation, answering how the CRL4CSA ligase is targeted to K1268 to initiate TC-NER.

    Evidence Genome-wide CRISPR screens, reciprocal Co-IP, and TC-NER/replication-stress assays in human cells (two companion papers)

    PMID:34108662 PMID:34108663

    Open questions at the time
    • Structural basis of CRL4CSA positioning not yet resolved
    • Mechanism of UVSSA/TFIIH recruitment downstream not detailed
  4. 2024 High

    Provided the structural mechanism: ELOF1 acts as an adaptor that docks UVSSA and CRL4CSA on arrested Pol II to activate ubiquitylation and orders a UVSSA element that blocks TFIIS reactivation, explaining how the repair-competent complex is locked in.

    Evidence Cryo-EM with biochemical assays and mutagenesis; yeast Elf1-Rad26-Pol II cryo-EM; Xenopus egg extract cell-free TC-NER reconstitution; cryo-EM/functional ordering of STK19 downstream

    PMID:38194460 PMID:38316879 PMID:39547228 PMID:39547229

    Open questions at the time
    • Precise XPD/TFIIH positioning step needed further definition
    • How ELOF1 dual function partitions between repair and normal transcription unresolved
  5. 2025 High

    Revealed ELOF1's role in normal transcription and immunity: it stabilizes paused RNAPII on chromatin as a platform for AID-driven mutagenesis, with RNAPII binding required for serine-5-phosphorylated pausing and antibody diversification.

    Evidence Mouse knockout, ChIP/ChIP-seq of RNAPII phospho-forms, proximity ligation, RNAPII-binding mutant complementation; native ChIP-cryoEM and IWS1-ELOF1 cryo-EM of elongation complexes

    PMID:40049160 PMID:40049162 PMID:40436841 PMID:40835814

    Open questions at the time
    • How ELOF1 selectively stabilizes pausing versus stimulating elongation not fully reconciled
    • Direct ELOF1-AID interaction interface undefined
  6. 2026 High

    Defined ELOF1 as a core component of the paused RNAPII complex that enhances DSIF/NELF-induced pausing and counteracts TFIIF, and placed it hierarchically downstream of CSB/CRL4CSA ubiquitylation in TFIIH-driven RNAPII clearance.

    Evidence Cryo-EM with in vitro reconstituted pausing assays and auxin-inducible degradation (preprint); time-resolved RNAPII clearance assays with TCR-factor KOs and VCP inhibition

    PMID:41554717 PMID:42244727

    Open questions at the time
    • Pausing data partly from a preprint awaiting peer review
    • Switch between pausing-stabilization and elongation-velocity roles not mechanistically defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ELOF1 integrates its opposing activities — stabilizing promoter-proximal pausing versus stimulating elongation, and repair-specific adaptor function versus constitutive elongation role — through a single RNAPII-binding interface remains unresolved.
  • No model explaining context-dependent switching of ELOF1 activities
  • Regulatory inputs that toggle ELOF1 function unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-168256 Immune System 2 R-HSA-74160 Gene expression (Transcription) 2
Complex memberships
RNA polymerase II elongation complexTC-NER complex (with CSB, CRL4CSA, UVSSA)promoter-proximal paused RNAPII complex (DSIF-NELF-ELOF1)

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 ELOF1 constitutively interacts with RNAPII close to K1268 and acts as a specificity factor that binds and positions the CRL4CSA ubiquitin ligase for optimal ubiquitylation of RNAPII at K1268 during transcription-coupled repair (TCR). ELOF1 loss prevents RNAPII ubiquitylation and downstream TCR factor assembly. CRISPR screen, Co-IP, drug-genetic interaction screening, cell biology Nature cell biology High 34108663
2021 ELOF1 promotes recruitment of TC-NER factors UVSSA and TFIIH to transcription-blocking lesions, enabling efficient repair and transcription resumption after DNA damage. ELOF1 also modulates transcription to protect cells against transcription-mediated replication stress and genome instability. Genome-wide CRISPR-Cas9 screen, immunofluorescence, transcription recovery assays, replication stress assays Nature cell biology High 34108662
2024 Cryo-EM structural analysis showed that ELOF1 serves as an adaptor to stably position UVSSA and CRL4CSA on arrested Pol II, leading to ligase neddylation and activation of Pol II ubiquitylation. In the presence of ELOF1, a TFIIS-like element in UVSSA becomes ordered and extends through the Pol II pore, preventing reactivation of Pol II by TFIIS. Cryo-electron microscopy, biochemical assays, cell biology, mutagenesis Nature structural & molecular biology High 38316879
2024 The yeast ELOF1 ortholog Elf1 promotes Rad26 (CSB ortholog) interactions with lesion-arrested Pol II. Cryo-EM structure of lesion-arrested Pol II-Rad26-Elf1 complex revealed that Elf1 induces additional interactions between Rad26 and lesion-arrested Pol II compared to other forms of stalled Pol II, facilitating TC-NER initiation. Cryo-EM structure determination, biochemical assays, genetic complementation Proceedings of the National Academy of Sciences of the United States of America High 38194460
2024 Cell-free reconstitution of TC-NER in frog egg extract demonstrated that ELOF1 is required for error-free repair of a site-specific lesion in a transcribed plasmid, establishing ELOF1 as an essential factor in the in vitro TC-NER reaction alongside CSB, CRL4CSA, and UVSSA. Cell-free TC-NER reconstitution in Xenopus egg extract, site-specific lesion plasmid, depletion assays, cryo-EM Cell High 39547228 39547229
2024 ELOF1 is required for RNAPII ubiquitylation but STK19 loss does not impair this step; STK19 acts downstream of ELOF1-facilitated ubiquitylation to facilitate clearance of lesion-stalled RNAPII. ELOF1 functions together with UVSSA and STK19 to properly recruit and position TFIIH for lesion processing. Cryo-EM, mutational analysis, live-cell imaging of RNAPII clearance, TC-NER assays Cell High 39547228 39547229
2025 ELOF1 stabilizes paused RNAPII at transcription barriers on antibody gene loci, providing a platform for AID-mediated transcription-coupled DNA damage. ELOF1 deficiency causes paused RNAPII to detach from chromatin, preventing recruitment of factors needed for both AID-induced damage and subsequent repair, resulting in defective class switch recombination and somatic hypermutation in mice. Genetic screen in B cells, mouse knockout, ChIP, proximity ligation, biochemical fractionation Molecular cell High 40049160 40049162
2025 ELOF1 must bind to RNAPII to serve as a proximity partner for AID and to function in somatic hypermutation and class switch recombination. Loss of ELOF1 reduces RNAPII pausing downstream of transcription start sites and reduces levels of serine-5 (but not serine-2) phosphorylated RNAPII throughout transcribed genes. Genetic complementation with RNAPII-binding mutants, ChIP-seq for RNAPII phospho-forms, proximity ligation assay Molecular cell High 40049160 40049162
2020 CRISPR screen identified ELOF1 as an RNAPII component whose loss modulates the response to transcription-blocking DNA-damaging agents, placing ELOF1 in the DNA damage response pathway for transcription-blocking lesions. CRISPR-Cas9 screen against genotoxic agents in RPE1 cells Cell Medium 32649862
2019 Mouse knockout of Elof1 results in peri-gastrulation lethality with developmental delay and morphological defects, and Elof1 regulates mutually exclusive exon use in vivo, suggesting a role in alternative splicing distinct from the yeast ortholog function. Mouse loss-of-function allele, phenotypic analysis, splice variant analysis PloS one Medium 31276560
2025 ChIP-cryoEM of transcribing RNAPII complexes isolated from human nuclei determined cryo-EM structures of RNAPII elongation complexes associated with genomic DNA in distinct forms, including complexes with ELOF1 and SPT4/5 or SPT6, revealing the structural context of ELOF1 within the elongation complex on chromatin. Chromatin immunopurification coupled to cryo-EM (ChIP-cryoEM) from human nuclei Nature communications Medium 40436841
2025 Cryo-EM structure of the activated Pol II elongation complex with IWS1 and ELOF1 showed that IWS1 transcription stimulation requires interactions with the RPB2 lobe and ELOF1, indicating ELOF1 cooperates with IWS1 to stimulate Pol II elongation velocity. Cryo-EM, in vitro transcription assays, rapid depletion (multi-omics kinetics) Nature communications Medium 40835814
2026 ELOF1 is a core component of the promoter-proximal paused RNAPII complex. ELOF1 is enriched at the promoter-proximal region of genes; its rapid degradation reduces pause duration in cells. In reconstituted assays, ELOF1 potently enhances pausing induced by DSIF and NELF at physiological nucleotide concentrations. Cryo-EM structures show that DSIF-NELF-ELOF1 sterically clashes with TFIIF on RNAPII, and RNAPII-DSIF-NELF-ELOF1 (but not RNAPII-DSIF-NELF) counteracts positive effects of TFIIF. Rapid protein degradation (auxin-inducible), ChIP-seq/PRO-seq, cryo-EM, in vitro reconstituted pausing assays bioRxivpreprint High 42244727
2026 RNAPII ubiquitylation by CSB and CRL4CSA is essential for RNAPII clearance from damage sites; downstream of this ubiquitylation, ELOF1 (together with UVSSA and STK19) is required for proper TFIIH recruitment and positioning, enabling XPD helicase-driven RNAPII dissociation as the primary rapid clearance route. Time-resolved RNAPII clearance assay, live-cell imaging, genetic KO of TCR factors, VCP inhibition Nature communications High 41554717

Source papers

Stage 0 corpus · 23 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A Genetic Map of the Response to DNA Damage in Human Cells. Cell 456 32649862
2021 ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation. Nature cell biology 92 34108663
2021 Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability. Nature cell biology 79 34108662
2024 Structural basis for RNA polymerase II ubiquitylation and inactivation in transcription-coupled repair. Nature structural & molecular biology 45 38316879
2024 STK19 positions TFIIH for cell-free transcription-coupled DNA repair. Cell 33 39547228
2024 STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair. Cell 29 39547229
2024 Elf1 promotes Rad26's interaction with lesion-arrested Pol II for transcription-coupled repair. Proceedings of the National Academy of Sciences of the United States of America 18 38194460
2024 Chromatin Transcription Elongation - A Structural Perspective. Journal of molecular biology 13 39476950
2020 RNA-Seq Analysis of Genetic and Transcriptome Network Effects of Dual-Trait Selection for Ethanol Preference and Withdrawal Using SOT and NOT Genetic Models. Alcoholism, clinical and experimental research 11 32090358
2025 Molecular model of TFIIH recruitment to the transcription-coupled repair machinery. Nature communications 10 40057514
2025 Transcription-coupled AID deamination damage depends on ELOF1-associated RNA polymerase II. Molecular cell 9 40049162
2024 STK19 positions TFIIH for cell-free transcription-coupled DNA repair. bioRxiv : the preprint server for biology 7 39091863
2025 Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination. Molecular cell 6 40049160
2025 The molecular basis of human transcription-coupled DNA repair. Nature cell biology 6 40764391
2025 Multiple structures of RNA polymerase II isolated from human nuclei by ChIP-CryoEM analysis. Nature communications 5 40436841
2025 IWS1 positions downstream DNA to globally stimulate Pol II elongation. Nature communications 3 40835814
2019 The elongation factor Elof1 is required for mammalian gastrulation. PloS one 3 31276560
2026 Hierarchical mechanisms control the clearance of DNA lesion-stalled RNA polymerase II. Nature communications 2 41554717
2025 Structure and function of IWS1 in transcription elongation. bioRxiv : the preprint server for biology 1 40909601
2024 Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination. bioRxiv : the preprint server for biology 1 39386505
2026 The role of transcription-coupled nucleotide excision repair (TC-NER) during mammalian forebrain development. Developmental biology 0 41921730
2026 Structure and function of IWS1 in transcription elongation. Nucleic acids research 0 42134803
2026 ELOF1 is a core component of the promoter-proximal paused RNA polymerase II complex. bioRxiv : the preprint server for biology 0 42244727

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