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Showing REV3L — REV3 is a alias.

REV3L

DNA polymerase zeta catalytic subunit · UniProt O60673

Length
3130 aa
Mass
352.8 kDa
Annotated
2026-06-10
84 papers in source corpus 31 papers cited in narrative 30 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

REV3L encodes the catalytic subunit of DNA polymerase zeta, a B-family translesion synthesis (TLS) polymerase that enables replication and repair synthesis across DNA lesions that block replicative polymerases (PMID:2676986, PMID:9618506). Its catalytic activity is mandatory: bypass of UV photoproducts, MMS, cisplatin, IR damage, and single bulky adducts depends on REV3L, and complete inactivation of the YGDTDS active-site aspartates phenocopies the null while a single-residue change is only hypomorphic (PMID:9447993, PMID:12805232, PMID:27481099). Pol zeta function requires partnership with REV7 (MAD2L2), which docks onto two defined motifs in REV3L (residues ~1877–1887 and ~1993–2003) and acts as an adaptor that also creates a platform for REV1 recruitment; disrupting both REV7-binding sites abolishes DNA damage tolerance and causes spontaneous chromosome breaks (PMID:20164194, PMID:25567983). REV3L is targeted to sites of stalled replication and repair through PCNA: an APIM motif mediates PCNA binding at replication foci, and monoubiquitinated PCNA is required for REV3L-dependent, recombination-independent interstrand crosslink repair in cooperation with REV1 (PMID:16571727, PMID:30597836). Beyond lesion bypass, REV3L sustains genome stability — it is required for stable replication through common fragile sites in G2/M, contributes error-prone repair synthesis during recombinational double-strand-break repair, participates in intra-S checkpoint activation, and cooperates with REV7 and REV1 (independently of shieldin) to protect and restart stalled forks against unrestrained MRE11 resection (PMID:12805232, PMID:23303771, PMID:36075897, PMID:38954736, PMID:12454056). These activities make REV3L indispensable for mammalian development: knockout mice die in mid-gestation with massive p53-independent apoptosis, double-strand breaks, and chromosomal aberrations (PMID:11050392, PMID:11050393, PMID:11050391, PMID:11884603). REV3L protein is stabilized by Taspase1-mediated cleavage, which prevents its ubiquitination and proteasomal degradation and is required for proper UV/cisplatin responses (PMID:32064513). De novo REV3L mutations cause a subset of Möbius syndrome, linking pol zeta to facial branchiomotor neuron development (PMID:26068067), and suppression of REV3L sensitizes tumors to cisplatin by abrogating TLS-mediated lesion bypass (PMID:21068376).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1979 High

    Established that a single gene controls the production of diverse UV-induced mutations, defining REV3 as a central mutagenesis factor rather than an allele-specific suppressor.

    Evidence UV mutagenesis assay across 12 cyc1 allele classes in rev3 mutant yeast

    PMID:385449

    Open questions at the time
    • Did not identify the gene product or its biochemical activity
    • No mechanistic link to replication
  2. 1989 High

    Identified REV3 as the catalytic subunit of a B-family DNA polymerase (pol zeta) required for mutagenesis but not viability in yeast, establishing the enzyme class.

    Evidence Gene cloning by complementation, sequencing, and deletion mutant analysis in S. cerevisiae

    PMID:2676986

    Open questions at the time
    • Polymerase activity inferred from sequence, not yet biochemically demonstrated
    • Lesion-bypass mechanism not directly shown
  3. 1981 Medium

    Separated REV3-dependent mutagenic bypass from error-free postreplication repair, clarifying which pathway REV3 acts in.

    Evidence Alkaline sucrose gradient sedimentation of UV-irradiated yeast DNA across repair-pathway mutants

    PMID:7038396

    Open questions at the time
    • Negative result; does not define the positive mechanism
    • Single-lab observation
  4. 1998 High

    Provided direct in vivo evidence that pol zeta performs translesion synthesis at a single defined adduct, converting genetic inference into mechanistic demonstration.

    Evidence Plasmid-based single-AAF-adduct TLS assay with strand-specific readout in REV3 vs rev3Δ yeast

    PMID:9447993

    Open questions at the time
    • Limited to one lesion type
    • Did not address recruitment to the lesion
  5. 1998 High

    Demonstrated functional conservation by cloning human REV3L and showing its loss abolishes UV mutagenesis, extending pol zeta TLS to human cells.

    Evidence cDNA cloning, sequencing of polymerase motifs, antisense knockdown and UV mutagenesis assay in human cells

    PMID:9618506

    Open questions at the time
    • Antisense knockdown incomplete
    • Subunit partners and recruitment in human cells not yet defined
  6. 2002 High

    Showed pol zeta also generates errors during recombinational DSB repair, broadening its role beyond lesion bypass to repair-synthesis mutagenesis.

    Evidence HO-endonuclease DSB induction with inverted-repeat substrate and mutation spectrum analysis in rev3 yeast

    PMID:12454056 PMID:9383049

    Open questions at the time
    • Mechanism of pol zeta engagement at repair-synthesis intermediates unclear
    • Yeast-specific quantitation
  7. 2002 High

    Established that mammalian Rev3l is essential for viability through its genome-protective function, with lethality driven by p53-independent damage-induced apoptosis.

    Evidence Targeted Rev3 knockout mice, cytogenetics, DSB assays, and p53 double-knockout rescue attempt; transgene complementation of blastocysts

    PMID:11050391 PMID:11050392 PMID:11050393 PMID:11884603 PMID:12051777

    Open questions at the time
    • Source of the lethal endogenous lesions not molecularly defined
    • Does not separate TLS from replication/repair roles in vivo
  8. 2003 High

    Resolved that pol zeta has multiple vertebrate roles — TLS, contribution to HR-mediated DSB repair, and suppression of spontaneous chromosomal instability — linking it directly to genome maintenance.

    Evidence DT40 REV3 knockout with damage-sensitivity, gene-targeting, SCE assays, and synthetic lethality with RAD54

    PMID:12805232

    Open questions at the time
    • Whether HR role is direct or indirect not resolved
    • Recruitment mechanism not addressed
  9. 2006 High

    Defined the recruitment switch: monoubiquitinated PCNA drives REV3-dependent, recombination-independent interstrand crosslink repair in cooperation with REV1.

    Evidence REV3/REV1 deletions in DT40 and MEFs with PCNA-ubiquitination mutant epistasis and ICL sensitivity assays

    PMID:16571727

    Open questions at the time
    • Did not map the REV3L motif mediating PCNA dependence
    • Stoichiometry with REV1 not defined
  10. 2008 Medium

    Linked pol zeta to cell-cycle-regulated chromatin loading and checkpoint signaling, identifying Chk2 phosphorylation of REV3 Ser995.

    Evidence Chromatin fractionation, cell cycle analysis, and in vitro Chk2 kinase assay

    PMID:18622427

    Open questions at the time
    • In vitro phosphorylation; in vivo functional consequence not established
    • Single lab
  11. 2010 High

    Defined the structural basis of subunit assembly, showing REV7 binds a REV3 fragment and simultaneously platforms REV1, casting REV7 as the adaptor that recruits pol zeta to lesions.

    Evidence X-ray crystallography of REV7/REV3-fragment complex with functional validation; siRNA TLS assays confirming both subunits required for UV-TLS

    PMID:20164194 PMID:21151666

    Open questions at the time
    • Structure limited to a short REV3 fragment
    • Full holoenzyme architecture unresolved
  12. 2010 Medium

    Provided therapeutic rationale by showing Rev3 suppression sensitizes resistant tumors to cisplatin and reduces drug-induced mutation, extending survival.

    Evidence shRNA Rev3 knockdown in a transplanted mouse lung adenocarcinoma model with cisplatin and survival endpoints

    PMID:21068376

    Open questions at the time
    • Knockdown not knockout
    • On-target specificity and systemic toxicity not assessed
  13. 2013 Medium

    Assigned REV3 a replication-completion role at common fragile sites in G2/M, connecting pol zeta to suppression of chromosomal breaks under replication stress.

    Evidence siRNA knockdown with metaphase CFS analysis, anaphase bridge scoring, FANCD2 immunofluorescence, and aphidicolin co-treatment in human cells

    PMID:23303771

    Open questions at the time
    • Knockdown rather than knockout
    • Direct catalytic action at CFS not biochemically shown
  14. 2015 High

    Mapped the REV7-binding interface to two REV3L motifs and demonstrated that REV7 association is required in vivo for UV/cisplatin resistance and prevention of chromosome breaks.

    Evidence Co-IP of full-length REV3L with REV7, site-directed mutagenesis of both binding sites, and functional complementation in human cells

    PMID:25567983

    Open questions at the time
    • Whether the two sites bind two REV7 molecules functionally distinct roles unresolved
    • Effect on catalytic processivity not measured
  15. 2015 Medium

    Linked REV3L to human neurodevelopmental disease, identifying de novo REV3L mutations in Möbius syndrome and a facial branchiomotor neuron proliferation defect in mice.

    Evidence Exome sequencing of MBS patients and analysis of Rev3l mutant mouse facial motor nucleus

    PMID:26068067

    Open questions at the time
    • Causal mechanism linking TLS loss to specific neuronal defect unclear
    • Genotype-phenotype range incomplete
  16. 2015 Medium

    Reported a non-nuclear role, with REV3L localizing to mitochondria, associating with POLG and mtDNA, and influencing OXPHOS.

    Evidence Subcellular fractionation, Co-IP with POLG, mtDNA association, and metabolic assays

    PMID:26462070

    Open questions at the time
    • Single lab; reciprocal validation of POLG interaction limited
    • Mechanistic role in mtDNA maintenance undefined
  17. 2016 High

    Established that catalytic activity is mandatory for REV3L's essential functions, distinguishing hypomorphic single-residue from null double-residue active-site mutations.

    Evidence Active-site mutagenesis with knock-in mouse strains, UVC sensitivity/mutagenesis and viability assays

    PMID:27481099

    Open questions at the time
    • Does not exclude structural (non-catalytic) contributions to some functions
    • Polymerase fidelity determinants not addressed
  18. 2018 Medium

    Identified the APIM motif as a direct PCNA-interaction module controlling REV3L recruitment to replication foci and TLS mutation specificity.

    Evidence YFP colocalization with PCNA, APIM competition, and APIM mutagenesis with mutation frequency/spectrum analysis across cell lines

    PMID:30597836

    Open questions at the time
    • Relationship between APIM and monoUb-PCNA dependence not integrated
    • Single lab
  19. 2020 High

    Revealed post-translational regulation: Taspase1 cleavage of REV3L blocks its ubiquitination and degradation, stabilizing the protein for DNA damage responses.

    Evidence Identification of Taspase1, endogenous cleavage-site knock-in, ubiquitination and proteasome-inhibitor assays, damage sensitivity in HCT116

    PMID:32064513

    Open questions at the time
    • How the cleavage fragments reassemble for catalysis unclear
    • Regulation of Taspase1 cleavage signaling not defined
  20. 2020 Medium

    Defined a dispensable internal region, showing the large intermediate domain is not required for UV-TLS, narrowing the functionally essential architecture.

    Evidence Domain-deletion complementation of Rev3KO MEFs with UV sensitivity and TLS assays

    PMID:33387704

    Open questions at the time
    • Domain may matter for non-UV functions
    • Single lab
  21. 2022 High

    Distinguished a fork-protection role: REV7 cooperates with REV3L and REV1 (not shieldin) to restart stalled forks and prevent MRE11-dependent over-resection.

    Evidence Genetic knockouts, single-molecule DNA fiber analysis, ssDNA/RPA immunofluorescence, and epistasis with shieldin and MRE11 inhibition

    PMID:36075897

    Open questions at the time
    • Whether catalytic activity is required for fork protection not resolved
    • Direct REV3L localization at forks not shown
  22. 2024 Medium

    Extended REV3 to checkpoint signaling, showing it is required for intra-S checkpoint Chk1 phosphorylation in parallel with the ATR-Chk1 axis.

    Evidence DT40 REV3 knockout with FUdR sensitivity, replication assays, Chk1 phosphorylation Western blots, and ATR/Chk1 inhibitor epistasis

    PMID:38954736

    Open questions at the time
    • Molecular link between pol zeta and checkpoint activation undefined
    • Single lab; lesion-specificity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How REV3L integrates its TLS, fork-protection, checkpoint, and BRCA1/RAD51-context functions, and whether these depend on a shared recruitment and catalytic mechanism, remains unresolved.
  • No unified model linking catalytic bypass to non-catalytic fork/checkpoint roles
  • BRCA1/SCAI-REV3 fork-breakage dependency reported only in a preprint (41394680)
  • Full pol zeta holoenzyme architecture and reassembly after Taspase1 cleavage unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 4 GO:0003677 DNA binding 2 GO:0016740 transferase activity 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 2
Partners
CHEK2MAD2L2PCNAPOLGREV1REV7TASP1
Complex memberships
DNA polymerase zeta (REV3L-REV7)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 REV3 encodes the catalytic subunit of a specialized DNA polymerase (DNA polymerase zeta) in S. cerevisiae that is required for UV-induced mutagenesis but is not essential for normal growth/replication; the protein shows sequence similarity to other B-family DNA polymerases including Epstein-Barr virus DNA polymerase and human DNA polymerase alpha. Gene cloning by complementation, nucleotide sequencing, deletion mutant analysis Journal of bacteriology High 2676986
1979 The REV3 gene function is required for UV-induced reversion of a wide variety of cyc1 alleles (ochre, amber, initiation, missense, and frameshift mutations) in S. cerevisiae, indicating REV3 is needed for production of diverse UV-induced mutational events. UV mutagenesis assay with rev3 mutant strains and multiple defined cyc1 alleles Genetics High 385449
1981 rev3 mutation does not affect postreplication repair in S. cerevisiae, distinguishing REV3-dependent mutagenic bypass from error-free postreplication repair pathways. Alkaline sucrose gradient sedimentation of DNA in UV-irradiated yeast; comparison of rad6, rad18, rev3, rad52 mutants Molecular & general genetics : MGG Medium 7038396
1998 Human REV3L encodes the catalytic subunit of a DNA polymerase zeta-type enzyme (3,130 residues); antisense-mediated reduction of REV3L in human cells abolishes UV-induced mutagenesis and confers slight UV sensitivity, demonstrating conservation of function from yeast. cDNA cloning, sequencing, antisense RNA expression in human cells, UV mutagenesis assay Proceedings of the National Academy of Sciences of the United States of America High 9618506
1998 In vivo biochemical evidence that Rev3 (DNA polymerase zeta) is specifically required for translesion synthesis (TLS) past a single N-2-acetylaminofluorene (AAF) adduct in S. cerevisiae; all TLS observed in REV3 cells was abolished in rev3Δ cells, with TLS being mostly error-free at this lesion. Plasmid-based TLS assay with single defined adduct, hybridization with strand-specific oligonucleotides to determine TLS vs. damage avoidance, comparison of REV3 vs. rev3Δ strains Molecular and cellular biology High 9447993
1997 REV3 (encoding a subunit of translesion DNA polymerase zeta) is responsible for the majority (~75%) of base substitution mutations associated with recombinational repair of HO endonuclease-induced double-strand breaks in S. cerevisiae, without affecting recombination frequency itself. Genetic epistasis: rev3 deletion strains with HO endonuclease-induced DSBs, trp1 reversion assay, recombination frequency measurement Genetics High 9383049
2000 Mouse Rev3l is essential for embryonic development; homozygous Rev3l knockout mice die at mid-gestation (~E9.5–12.5) with retarded growth and disorganized tissues, demonstrating that polymerase zeta function is indispensable for mammalian cell viability during development, unlike in yeast. Targeted gene disruption in mice (two exons containing conserved polymerase motifs replaced with beta-gal reporter/neomycin cassette), embryo staging and histology Current biology : CB High 11050391 11050392 11050393
2000 Rev3l-deficient mouse embryos lack non-erythroid haematopoietic cells, Rev3l-/- haematopoietic precursors cannot expand in vitro, fibroblasts cannot be derived, and Rev3l-/- ES cells cannot be obtained, indicating a cell-autonomous requirement for Rev3l in mammalian cell proliferation. Targeted Rev3l knockout, in vitro culture of haematopoietic precursors and blastocysts, attempt to derive ES cells Current biology : CB High 11050393
2002 Absence of mouse Rev3 leads to massive apoptosis in all embryonic lineages and accumulation of DNA double-strand breaks and chromatid/chromosome aberrations; p53 elevation occurs but embryonic lethality is not rescued by p53 deficiency, indicating p53-independent apoptotic death from unreplicated DNA damage. Targeted Rev3 disruption in mice, histochemistry for apoptosis, comet/PFGE for DSBs, cytogenetic analysis, p53 double-knockout Molecular and cellular biology High 11884603
2002 REV3 transgene expression restores survival and outgrowth of Rev3-/- blastocysts in culture and suppresses apoptosis in E7.5 Rev3-/- embryos, confirming the cell-autonomous requirement for REV3; p53 deficiency does not rescue the embryonic lethality. Rev3 transgene complementation of Rev3-/- blastocysts, p53/Rev3 double knockout, blastocyst culture Biochemical and biophysical research communications Medium 12051777
2003 Rev3 (pol zeta catalytic subunit) plays multiple roles in vertebrate cells: required for TLS past UV, MMS, cisplatin and IR damage; involved in homologous recombination-mediated DSB repair (reduced gene targeting efficiency in REV3-/- DT40 cells); REV3/RAD54 double mutants are synthetic lethal; REV3 loss increases sister chromatid exchanges and chromosomal breaks even without exogenous damage. Gene disruption in chicken DT40 cells, DNA damage sensitivity assays, gene targeting frequency measurement, SCE analysis, synthetic lethality with RAD54 knockout The EMBO journal High 12805232
2006 Rev3 plays a major role in recombination-independent interstrand crosslink (ICL) repair; monoubiquitinated PCNA is required for this Rev3-dependent ICL repair pathway, indicating Rev3 is recruited via the PCNA ubiquitination switch during DNA repair synthesis; Rev1 cooperates with Rev3 in recombination-independent ICL repair. REV3 and REV1 deletion in DT40 and mouse embryonic fibroblasts, ICL sensitivity assays, PCNA ubiquitination-defective mutant analysis, mutation spectrum analysis The Journal of biological chemistry High 16571727
2010 Crystal structure of human REV7 in complex with a human REV3 fragment (residues 1847–1898) reveals the molecular mechanism of REV7-REV3 interaction and shows that this interface also creates a structural platform for REV1 binding, positioning REV7 as an adaptor protein recruiting pol zeta to lesion sites. X-ray crystallography of REV7/REV3-fragment complex, structural analysis, functional validation of REV7-mediated interactions in DNA damage tolerance The Journal of biological chemistry High 20164194
2015 Human REV3L contains two REV7-binding sites (residues 1877–1887 and residues 1993–2003); mutation of both sites eliminates the REV3L-REV7 interaction; both binding sites are necessary for preventing spontaneous chromosome breaks and conferring resistance to UV and cisplatin in vivo, demonstrating that REV7 association with pol zeta is required for DNA damage tolerance. Co-immunoprecipitation of full-length REV3L with REV7 in vivo, site-directed mutagenesis of REV7-binding sites, functional complementation assay measuring UV/cisplatin resistance and chromosome break frequency Nucleic acids research High 25567983
2013 REV3 (catalytic subunit of pol zeta) is required for stable replication of common fragile sites (CFSs) during G2/M; REV3 depletion causes anaphase bridges, chromosomal breaks/gaps, and CFS expression that is enhanced by aphidicolin-induced replication stress and associated with FANCD2 focus formation; long-term REV3 depletion causes massive genomic instability and cell cycle arrest. siRNA knockdown of REV3, metaphase CFS analysis, anaphase bridge scoring, FANCD2 immunofluorescence, aphidicolin co-treatment Nucleic acids research Medium 23303771
2015 REV3L localizes to mammalian mitochondria; it associates with mitochondrial DNA polymerase gamma (POLG) and with mitochondrial DNA; REV3L inactivation reduces mitochondrial membrane potential and OXPHOS activity and increases glucose consumption. Subcellular fractionation, co-immunoprecipitation with POLG, mitochondrial DNA association assay, metabolic assays (membrane potential, OXPHOS activity) PloS one Medium 26462070
2016 A catalytic site point mutation in REV3L (mutation of one Asp in the invariant YGDTDS motif) is hypomorphic rather than null in both yeast and mouse, moderately impairing enzymatic activity but not viability; simultaneous mutation of both Asp residues (ATA) phenocopies the Rev3l knockout, demonstrating that catalytic activity is mandatory for REV3L's essential functions. Site-directed mutagenesis of catalytic residues, knock-in mouse strains, UVC sensitivity and mutagenesis assays, viability assessment DNA repair High 27481099
2018 REV3L contains a functional AlkB homolog 2 PCNA-interacting protein motif (APIM) that mediates interaction with PCNA at replication foci; overexpression of APIM-mutated REV3L significantly alters UV-induced mutation frequencies and spectra compared to wild-type REV3L, indicating that APIM-mediated PCNA interaction is required for proper pol zeta function and TLS specificity. YFP fusion colocalization with PCNA in replication foci, APIM competition experiment, site-directed APIM mutagenesis with mutation frequency and spectrum analysis in multiple cell lines International journal of molecular sciences Medium 30597836
2020 Human REV3L undergoes site-specific proteolytic cleavage by Taspase1 (TASP1), generating an N-terminal ~70 kDa fragment and a C-terminal polymerase catalytic domain-containing polypeptide; this cleavage prevents ubiquitination and proteasomal degradation of REV3L, thereby stabilizing the protein; point mutations in the endogenous REV3L cleavage site impair cellular responses to UV and cisplatin. Identification of Taspase1 as the cleavage enzyme, endogenous REV3L cleavage site mutagenesis (knock-in HCT116 cells), ubiquitination assay, proteasome inhibitor experiments, DNA damage sensitivity assays Nucleic acids research High 32064513
2008 REV3 protein accumulates on chromatin in late S/G2 phase in untreated cells and in response to clastogenic DNA damage; serine 995 of REV3 is phosphorylated in vitro by checkpoint kinase Chk2, suggesting REV3 is a substrate of the DSB-inducible checkpoint kinase. Chromatin fractionation, cell cycle analysis, in vitro Chk2 kinase assay with REV3 peptide/protein Oncogene Medium 18622427
2010 Suppression of Rev3 (pol zeta catalytic subunit) in drug-resistant mouse lung adenocarcinoma tumors causes pronounced sensitivity to cisplatin and significantly extends overall survival in recipient mice; Rev3-deficient cells also show reduced cisplatin-induced mutation. shRNA-mediated Rev3 knockdown in transplanted lung tumor model in mice, cisplatin treatment, survival analysis, mutation frequency measurement Proceedings of the National Academy of Sciences of the United States of America Medium 21068376
2010 siRNA targeting REV3 or REV7 largely abolishes UV-induced translesion replication (TLS) in HeLa cells, confirming that both subunits of pol zeta are required for mutagenic TLS; REV1 siRNA also abrogates UV-TLS, while Poleta and Polkappa contribute partially. siRNA knockdown of TLS polymerase subunits, alkaline sucrose density gradient sedimentation to measure TLS in UV-irradiated HeLa cells Journal of nucleic acids Medium 21151666
2022 MAD2L2 (REV7) cooperates specifically with REV3L and REV1 (rather than with shieldin) to protect and restart stalled replication forks; MAD2L2 loss leads to MRE11-dependent uncontrolled resection of stalled forks and ssDNA accumulation; this fork protection role of MAD2L2 is independent of the shieldin complex. Genetic knockouts in human cells, single-molecule DNA fiber analysis, immunofluorescence for ssDNA/RPA, genetic epistasis with shieldin and MRE11 inhibitors Nature communications High 36075897
2024 REV3 is required for both translesion synthesis over FUdR-damaged templates and intra-S phase checkpoint activation in response to FUdR; REV3-/- cells show defective Chk1 phosphorylation and defective early S-phase arrest; this checkpoint function acts in parallel with the canonical ATR-Chk1 pathway. REV3 knockout in DT40 cells, FUdR sensitivity screen, replication assays on damaged templates, cell cycle analysis, Chk1 phosphorylation assay by Western blot, ATR/Chk1 inhibitor epistasis PLoS genetics Medium 38954736
2015 De novo mutations in REV3L cause a subset of Möbius syndrome (MBS) cases; analysis of Rev3l mutant mice shows that REV3L disruption affects facial branchiomotor neuron proliferation, converging with the PLXND1 (neural migration) pathway at the facial branchiomotor nucleus. Exome sequencing of MBS patients identifying de novo REV3L mutations, analysis of Rev3l mutant mouse facial motor nucleus development Nature communications Medium 26068067
2002 REV3 accounts for approximately 75% of break-repair-induced mutations (BRIMs) including ~90% of base substitutions during recombinational repair of DSBs in S. cerevisiae; REV3 is not required for recombination itself but introduces errors during repair synthesis; frameshift BRIMs are REV3-independent. Inverted-repeat recombination substrate with HO-endonuclease DSB induction, mutation spectrum analysis in rev3 deletion strains Genetics High 12454056
2020 A large intermediate domain (residues 532–1793) of mouse REV3 is dispensable for UV-induced translesion replication in cultured cells; stable transformants expressing Rev3 with deleted intermediate domain show comparable UV sensitivity and UV-TLS activity to wild-type cells. REV3 deletion construct complementation of Rev3KO mouse embryo fibroblasts, UV sensitivity assay, alkaline sucrose density gradient sedimentation for TLS DNA repair Medium 33387704
2025 REV7 inhibits mitotic entry in response to DNA replication stress in chicken and human cells, functioning as a checkpoint protein; this function depends on REV7's ability to homodimerize and bind its ligands (consistent with HORMA protein conformational change mechanism); even in unchallenged cells, REV7 deletion leads to premature mitotic entry, suggesting REV7/REV3L monitors ongoing DNA replication. REV7 gene deletion in chicken and human cells, mitotic entry assays under replication stress, analysis of REV7 dimerization mutants, cell cycle profiling Cell reports Medium 40106439
2025 BRCA1/RAD51 regulation creates dependency on SCAI and REV3 for stalled replication fork maintenance; in the absence of SCAI and REV3, BRCA1 drives SLX4-SLX1-ERCC1-mediated DNA break formation at stalled forks; loss of fork reversal factors leads to additive REV3-dependent fork breakage dependent on RAD51 activity. Genetic knockouts, DNA fiber analysis, phospho-RPA/γH2AX foci, epistasis with BRCA1 domain mutants and fork reversal factor knockouts bioRxivpreprint Low 41394680
2023 In undamaged human cancer cells, MAD2B (REV7) exists in a complex with pol zeta-Rev1 and APC/C subunit Cdc27; following cisplatin-induced DNA damage, Cdc20 is recruited to this complex and MAD2B-dependent APC/C activation (ubiquitination activity) is increased. Co-immunoprecipitation, in vitro ubiquitination assay, immunofluorescence for DNA damage recruitment The Korean journal of physiology & pharmacology Low 37641805

Source papers

Stage 0 corpus · 84 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 A human homolog of the Saccharomyces cerevisiae REV3 gene, which encodes the catalytic subunit of DNA polymerase zeta. Proceedings of the National Academy of Sciences of the United States of America 288 9618506
1989 REV3, a Saccharomyces cerevisiae gene whose function is required for induced mutagenesis, is predicted to encode a nonessential DNA polymerase. Journal of bacteriology 246 2676986
1981 Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations. Molecular & general genetics : MGG 237 7038396
1997 A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae. Genetics 175 9383049
2003 Multiple roles of Rev3, the catalytic subunit of polzeta in maintaining genome stability in vertebrates. The EMBO journal 174 12805232
2010 Suppression of Rev3, the catalytic subunit of Pol{zeta}, sensitizes drug-resistant lung tumors to chemotherapy. Proceedings of the National Academy of Sciences of the United States of America 157 21068376
2000 Disruption of the developmentally regulated Rev3l gene causes embryonic lethality. Current biology : CB 144 11050392
2000 Disruption of the Rev3l-encoded catalytic subunit of polymerase zeta in mice results in early embryonic lethality. Current biology : CB 143 11050393
2000 Disruption of mouse polymerase zeta (Rev3) leads to embryonic lethality and impairs blastocyst development in vitro. Current biology : CB 129 11050391
2010 Crystal structure of human REV7 in complex with a human REV3 fragment and structural implication of the interaction between DNA polymerase zeta and REV1. The Journal of biological chemistry 107 20164194
2002 The roles of REV3 and RAD57 in double-strand-break-repair-induced mutagenesis of Saccharomyces cerevisiae. Genetics 93 12454056
1994 Specificity of the yeast rev3 delta antimutator and REV3 dependency of the mutator resulting from a defect (rad1 delta) in nucleotide excision repair. Genetics 92 8088509
1979 Ultraviolet-induced reversion of cyc1 alleles in radiation-sensitive strains of yeast. III. rev3 mutant strains. Genetics 90 385449
2006 REV3 and REV1 play major roles in recombination-independent repair of DNA interstrand cross-links mediated by monoubiquitinated proliferating cell nuclear antigen (PCNA). The Journal of biological chemistry 79 16571727
2002 Involvement of mouse Rev3 in tolerance of endogenous and exogenous DNA damage. Molecular and cellular biology 77 11884603
2007 Double-strand breaks induce homologous recombinational repair of interstrand cross-links via cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi anemia pathway. DNA repair 72 17669695
1998 Analysis of damage tolerance pathways in Saccharomyces cerevisiae: a requirement for Rev3 DNA polymerase in translesion synthesis. Molecular and cellular biology 72 9447993
2015 De novo mutations in PLXND1 and REV3L cause Möbius syndrome. Nature communications 71 26068067
2013 Rev3, the catalytic subunit of Polζ, is required for maintaining fragile site stability in human cells. Nucleic acids research 71 23303771
2009 REV3L confers chemoresistance to cisplatin in human gliomas: the potential of its RNAi for synergistic therapy. Neuro-oncology 61 19289490
2015 REV7 is essential for DNA damage tolerance via two REV3L binding sites in mammalian DNA polymerase ζ. Nucleic acids research 58 25567983
2015 c-Myc-miR-29c-REV3L signalling pathway drives the acquisition of temozolomide resistance in glioblastoma. Brain : a journal of neurology 57 26450587
2012 REV3L 3'UTR 460 T>C polymorphism in microRNA target sites contributes to lung cancer susceptibility. Oncogene 56 22349819
1995 Specificities of the Saccharomyces cerevisiae rad6, rad18, and rad52 mutators exhibit different degrees of dependence on the REV3 gene product, a putative nonessential DNA polymerase. Genetics 53 7498727
2011 Inhibition of REV3 expression induces persistent DNA damage and growth arrest in cancer cells. Neoplasia (New York, N.Y.) 50 22028621
2015 Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome. PloS one 48 26462070
2009 Xpf and not the Fanconi anaemia proteins or Rev3 accounts for the extreme resistance to cisplatin in Dictyostelium discoideum. PLoS genetics 47 19763158
2009 The translesion polymerase Rev3L in the tolerance of alkylating anticancer drugs. Molecular pharmacology 43 19641035
1999 Molecular cloning, expression and chromosomal localisation of the mouse Rev3l gene, encoding the catalytic subunit of polymerase zeta. Mutation research 41 10102037
2015 REV3L, a promising target in regulating the chemosensitivity of cervical cancer cells. PloS one 39 25781640
2020 Circular RNA PRMT5 confers cisplatin-resistance via miR-4458/REV3L axis in non-small-cell lung cancer. Cell biology international 38 32808744
2000 Saccharomyces cerevisiae lacking Snm1, Rev3 or Rad51 have a normal S-phase but arrest permanently in G2 after cisplatin treatment. Mutation research 37 10980408
2008 Novel evidences for a tumor suppressor role of Rev3, the catalytic subunit of Pol zeta. Oncogene 36 18622427
1992 The REV3 gene of Saccharomyces cerevisiae is transcriptionally regulated more like a repair gene than one encoding a DNA polymerase. Molecular & general genetics : MGG 36 1494346
2004 Immortalized mouse cell lines that lack a functional Rev3 gene are hypersensitive to UV irradiation and cisplatin treatment. DNA repair 35 15177183
1998 Alternative splicing, genomic structure, and fine chromosome localization of REV3L. Cytogenetics and cell genetics 35 9925914
2015 REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells. Oncology reports 29 26165320
2002 An essential role for REV3 in mammalian cell survival: absence of REV3 induces p53-independent embryonic death. Biochemical and biophysical research communications 27 12051777
2009 Purification, crystallization and initial X-ray diffraction study of human REV7 in complex with a REV3 fragment. Acta crystallographica. Section F, Structural biology and crystallization communications 26 20054135
2016 Exome sequencing reveals recurrent REV3L mutations in cisplatin-resistant squamous cell carcinoma of head and neck. Scientific reports 25 26790612
2001 The error-prone DNA polymerase zeta catalytic subunit (Rev3) gene is ubiquitously expressed in normal and malignant human tissues. International journal of oncology 23 11115544
2019 miR-145 Regulates the sensitivity of esophageal squamous cell carcinoma cells to 5-FU via targeting REV3L. Pathology, research and practice 22 31072625
2001 Isolation and genetic characterisation of the Drosophila homologue of (SCE)REV3, encoding the catalytic subunit of DNA polymerase zeta. Mutation research 21 11267835
2020 Lnc-PICSAR contributes to cisplatin resistance by miR-485-5p/REV3L axis in cutaneous squamous cell carcinoma. Open life sciences 20 33817237
2014 Berberine induces double-strand DNA breaks in Rev3 deficient cells. Molecular medicine reports 20 24584584
2022 MAD2L2 promotes replication fork protection and recovery in a shieldin-independent and REV3L-dependent manner. Nature communications 19 36075897
2017 MicroRNA-340 inhibits the proliferation and promotes the apoptosis of colon cancer cells by modulating REV3L. Oncotarget 19 29435169
2016 REV3L, the catalytic subunit of DNA polymerase ζ, is involved in the progression and chemoresistance of esophageal squamous cell carcinoma. Oncology reports 19 26752104
2018 MicroRNA‑29a enhances cisplatin sensitivity in non‑small cell lung cancer through the regulation of REV3L. Molecular medicine reports 18 30535450
2017 Hypermutation signature reveals a slippage and realignment model of translesion synthesis by Rev3 polymerase in cisplatin-treated yeast. Proceedings of the National Academy of Sciences of the United States of America 18 28223526
2018 APIM-Mediated REV3L⁻PCNA Interaction Important for Error Free TLS Over UV-Induced DNA Lesions in Human Cells. International journal of molecular sciences 17 30597836
2019 Blood mRNA expression of REV3L and TYMS as potential predictive biomarkers from platinum-based chemotherapy plus pemetrexed in non-small cell lung cancer patients. Cancer chemotherapy and pharmacology 16 31832811
2017 Knockdown of REV3 synergizes with ATR inhibition to promote apoptosis induced by cisplatin in lung cancer cells. Journal of cellular physiology 16 28075014
2014 Whole genome RNAi screens reveal a critical role of REV3 in coping with replication stress. Molecular oncology 14 25113059
2007 Error-free RAD52 pathway and error-prone REV3 pathway determines spontaneous mutagenesis in Saccharomyces cerevisiae. Genes & genetic systems 14 17396018
2003 Response of human REV3 gene to gastric cancer inducing carcinogen N-methyl-N'-nitro-N-nitrosoguanidine and its role in mutagenesis. World journal of gastroenterology 14 12717825
2005 Epistatic participation of REV1 and REV3 in the formation of UV-induced frameshift mutations in cell cycle-arrested yeast cells. Mutation research 13 16154164
1998 The uvsI gene of Aspergillus nidulans required for UV-mutagenesis encodes a homolog to REV3, a subunit of the DNA polymerase zeta of yeast involved in translesion DNA synthesis. FEMS microbiology letters 12 9675845
1999 REV3 is required for spontaneous but not methylation damage-induced mutagenesis of Saccharomyces cerevisiae cells lacking O6-methylguanine DNA methyltransferase. Mutation research 9 10656494
2024 REV3 promotes cellular tolerance to 5-fluorodeoxyuridine by activating translesion DNA synthesis and intra-S checkpoint. PLoS genetics 8 38954736
2021 Circ_0023984 Facilitates Esophageal Squamous Cell Carcinoma Progression by Regulating miR-433-3p/REV3L Axis. Digestive diseases and sciences 8 33725240
2016 A single aspartate mutation in the conserved catalytic site of Rev3L generates a hypomorphic phenotype in vivo and in vitro. DNA repair 8 27481099
2012 Crystallization and X-ray diffraction analysis of the ternary complex of the C-terminal domain of human REV1 in complex with REV7 bound to a REV3 fragment involved in translesion DNA synthesis. Acta crystallographica. Section F, Structural biology and crystallization communications 8 22869133
2010 Rev1, Rev3, or Rev7 siRNA Abolishes Ultraviolet Light-Induced Translesion Replication in HeLa Cells: A Comprehensive Study Using Alkaline Sucrose Density Gradient Sedimentation. Journal of nucleic acids 8 21151666
2020 Site-specific proteolytic cleavage prevents ubiquitination and degradation of human REV3L, the catalytic subunit of DNA polymerase ζ. Nucleic acids research 7 32064513
2018 Absence of REV3L promotes p53-regulated cancer cell metabolism in cisplatin-treated lung carcinoma cells. Biochemical and biophysical research communications 7 29307819
2011 Caffeine abolishes the ultraviolet-induced REV3 translesion replication pathway in mouse cells. International journal of molecular sciences 7 22272088
2004 Response of REV3 promoter to N-methyl-N'-nitro-N-nitrosoguanidine. Mutation research 7 15135640
1987 Mitochondrial mutagenesis in yeast: mutagenic specificity of EMS and the effects of RAD9 and REV3 gene products. Mutation research 7 3614243
2009 Near-full-length REV3L appears to be a scarce maternal factor in Xenopus laevis eggs that changes qualitatively in early embryonic development. DNA repair 5 19896909
2021 REV3L single nucleotide variants lead to increased susceptibility towards non-small cell lung cancer in the population of Jammu and Kashmir. Cancer epidemiology 4 34655923
2020 Mutant POLQ and POLZ/REV3L DNA polymerases may contribute to the favorable survival of patients with tumors with POLE mutations outside the exonuclease domain. BMC medical genetics 4 32838755
2020 Nucleotide Excision Repair, XPA-1, and the Translesion Synthesis Complex, POLZ-1 and REV-1, Are Critical for Interstrand Cross-Link Repair in Caenorhabditis elegans Germ Cells. Biochemistry 4 32945661
2023 Mad2B forms a complex with Cdc20, Cdc27, Rev3 and Rev1 in response to cisplatin-induced DNA damage. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 3 37641805
2022 DNA Polymerase ζ without the C-Terminus of Catalytic Subunit Rev3 Retains Characteristic Activity, but Alters Mutation Specificity of Ultraviolet Radiation in Yeast. Genes 3 36140745
2025 REV7 functions with REV3 as a checkpoint protein delaying mitotic entry until DNA replication is completed. Cell reports 2 40106439
2021 Developmental delay with hypotrophy associated with homozygous functionally relevant REV3L variant. Journal of molecular medicine (Berlin, Germany) 2 33474647
2003 [Cloning and bioinformatics of human REV3 gene promoter region and its response to carcinogen N-methyl-N'-nitro-N-nitrosoguanidine]. Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 2 14610737
2023 Backbone and ILV side-chain methyl NMR resonance assignments of human Rev7/Rev3-RBM1 and Rev7/Rev3-RBM2 complexes. Biomolecular NMR assignments 1 37129702
2020 A large intermediate domain of vertebrate REV3 protein is dispensable for ultraviolet-induced translesion replication. DNA repair 1 33387704
2017 A comprehensive experiment for molecular biology: Determination of single nucleotide polymorphism in human REV3 gene using PCR-RFLP. Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology 1 28145107
2025 "Chance and Necessity" on the Molecular Evolution of REV3 (a Catalytic Subunit of DNA Polymerase ζ)-The Dual Roles of Translesion and Neuronal Extension. Genes to cells : devoted to molecular & cellular mechanisms 0 39822052
2025 The BRCA1- RAD51 Axis Regulates SCAI/REV3 Dependent Replication Fork Maintenance. bioRxiv : the preprint server for biology 0 41394680
2010 [Roles of REV3 in proliferation and genomic stability of colon carcinoma cells]. Yi chuan = Hereditas 0 20466635

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