Gene Symbol: Rev3l
Description: REV3 like, DNA directed polymerase zeta catalytic subunit
Alias: Rev, Rev3, Sez4, DNA polymerase zeta catalytic subunit, REV3-like, catalytic subunit of DNA polymerase zeta RAD54 like, seizure-related protein 4
Species: mouse
Products:     Rev3l

Top Publications

  1. Wittschieben J, Reshmi S, Gollin S, Wood R. Loss of DNA polymerase zeta causes chromosomal instability in mammalian cells. Cancer Res. 2006;66:134-42 pubmed
    b>Rev3L encodes the catalytic subunit of DNA polymerase zeta (pol zeta) in mammalian cells. In yeast, pol zeta helps cells bypass sites of DNA damage that can block replication enzymes...
  2. Bemark M, Khamlichi A, Davies S, Neuberger M. Disruption of mouse polymerase zeta (Rev3) leads to embryonic lethality and impairs blastocyst development in vitro. Curr Biol. 2000;10:1213-6 pubmed
    ..Here, we have focused on polymerase zeta. This was first described as a non-essential product of the yeast REV3/REV7 genes involved in UV-induced mutagenesis, and was later implicated in trans-lesion synthesis [4,5]...
  3. Esposito G, Godindagger I, Klein U, Yaspo M, Cumano A, Rajewsky K. Disruption of the Rev3l-encoded catalytic subunit of polymerase zeta in mice results in early embryonic lethality. Curr Biol. 2000;10:1221-4 pubmed that, unlike in yeast where the REV3 gene is not essential for life [4], disruption of the mouse homologue (Rev3l) resulted in early embryonic lethality...
  4. Wittschieben J, Patil V, Glushets V, Robinson L, Kusewitt D, Wood R. Loss of DNA polymerase zeta enhances spontaneous tumorigenesis. Cancer Res. 2010;70:2770-8 pubmed publisher
    ..Although the DNA polymerase zeta (polzeta) catalytic subunit REV3L is important in defense against genotoxins, little is known of its biological function...
  5. Zander L, Bemark M. Immortalized mouse cell lines that lack a functional Rev3 gene are hypersensitive to UV irradiation and cisplatin treatment. DNA Repair (Amst). 2004;3:743-52 pubmed
    The catalytic subunit of polymerase zeta is encoded from the Rev3 gene. The enzyme is conserved through eukaryotic evolution and its main function appears to be translesion synthesis (TLS) over damaged bases that stall DNA replication...
  6. Schenten D, Kracker S, Esposito G, Franco S, Klein U, Murphy M, et al. Pol zeta ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stability. J Exp Med. 2009;206:477-90 pubmed publisher
    ..and possible contribution to DNA double-strand break (DSB) repair in class switch recombination (CSR), we ablated Rev3, the catalytic subunit of Pol zeta, selectively in mature B cells in vivo...
  7. Jansen J, Tsaalbi Shtylik A, Hendriks G, Verspuy J, Gali H, Haracska L, et al. Mammalian polymerase zeta is essential for post-replication repair of UV-induced DNA lesions. DNA Repair (Amst). 2009;8:1444-51 pubmed publisher
    ..investigated replication of ultraviolet light-damaged DNA templates in mouse embryonic fibroblasts deficient for Rev3, the catalytic subunit of polymerase zeta...
  8. Shachar S, Ziv O, Avkin S, Adar S, Wittschieben J, Reissner T, et al. Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals. EMBO J. 2009;28:383-93 pubmed publisher
    ..A single gene, REV3L, encoding the catalytic subunit of DNA polymerase zeta (pol zeta), was found to have a pivotal role in TLS, being ..
  9. Shen X, Jun S, O Neal L, Sonoda E, Bemark M, Sale J, et al. REV3 and REV1 play major roles in recombination-independent repair of DNA interstrand cross-links mediated by monoubiquitinated proliferating cell nuclear antigen (PCNA). J Biol Chem. 2006;281:13869-72 pubmed
    ..the role of lesion bypass polymerases in ICL repair, we investigated recombination-independent repair of ICLs in REV3 and REV1 deletion mutants constructed in avian DT40 cells and mouse embryonic fibroblast cells...

More Information


  1. Van Sloun P, Romeijn R, Eeken J. Molecular cloning, expression and chromosomal localisation of the mouse Rev3l gene, encoding the catalytic subunit of polymerase zeta. Mutat Res. 1999;433:109-16 pubmed
    ..The mouse homolog of this gene, Rev3l, was cloned and sequenced. The gene encodes a putative protein of 3122 amino acids...
  2. Wittschieben J, Shivji M, Lalani E, Jacobs M, Marini F, Gearhart P, et al. Disruption of the developmentally regulated Rev3l gene causes embryonic lethality. Curr Biol. 2000;10:1217-20 pubmed
    ..motifs were replaced by a cassette encoding G418 resistance and beta-galactosidase, under the control of the Rev3l promoter...
  3. Lin Y, Owen N, Minko I, Lange S, Tomida J, Li L, et al. DNA polymerase ζ limits chromosomal damage and promotes cell survival following aflatoxin exposure. Proc Natl Acad Sci U S A. 2016;113:13774-13779 pubmed
    ..Following challenge with AFB1, survival of mouse cells deficient in pol ζ (Rev3L-/-) was significantly reduced relative to Rev3L+/- cells or Rev3L-/- cells ..
  4. Daly J, Bebenek K, Watt D, Richter K, Jiang C, Zhao M, et al. Altered Ig hypermutation pattern and frequency in complementary mouse models of DNA polymerase ζ activity. J Immunol. 2012;188:5528-37 pubmed publisher
    ..Combined, these data are best explained by a direct role for DNA polymerase ζ in Ig hypermutation. ..
  5. Doles J, Oliver T, Cameron E, Hsu G, Jacks T, Walker G, et al. Suppression of Rev3, the catalytic subunit of Pol{zeta}, sensitizes drug-resistant lung tumors to chemotherapy. Proc Natl Acad Sci U S A. 2010;107:20786-91 pubmed publisher
    ..In the presence of reduced levels of Rev3, an essential component of Pol?, tumors exhibited pronounced sensitivity to cisplatin, leading to a significant ..
  6. McCulloch S, Kokoska R, Garg P, Burgers P, Kunkel T. The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases delta and eta. Nucleic Acids Res. 2009;37:2830-40 pubmed publisher
    ..The fact that yeast and mammalian Pol eta have intrinsically different catalytic properties has potential biological implications. ..
  7. Diaz M, Watson N, Turkington G, Verkoczy L, Klinman N, McGregor W. Decreased frequency and highly aberrant spectrum of ultraviolet-induced mutations in the hprt gene of mouse fibroblasts expressing antisense RNA to DNA polymerase zeta. Mol Cancer Res. 2003;1:836-47 pubmed
    ..The catalytic subunit of pol zeta is encoded by the Rev3 gene...
  8. Lange S, Tomida J, Boulware K, Bhetawal S, Wood R. The Polymerase Activity of Mammalian DNA Pol ζ Is Specifically Required for Cell and Embryonic Viability. PLoS Genet. 2016;12:e1005759 pubmed publisher
    DNA polymerase ζ (pol ζ) is exceptionally important for maintaining genome stability. Inactivation of the Rev3l gene encoding the polymerase catalytic subunit causes a high frequency of chromosomal breaks, followed by lethality in ..
  9. Yoon J, Prakash L, Prakash S. Error-free replicative bypass of (6-4) photoproducts by DNA polymerase zeta in mouse and human cells. Genes Dev. 2010;24:123-8 pubmed publisher
    ..We verify and extend these observations in mouse cells and conclude that, in human cells, TLS during replication can be markedly error-free even opposite a highly distorting DNA lesion. ..
  10. Tomas Roca L, Tsaalbi Shtylik A, Jansen J, Singh M, Epstein J, Altunoglu U, et al. De novo mutations in PLXND1 and REV3L cause Möbius syndrome. Nat Commun. 2015;6:7199 pubmed publisher
    ..Here, we report de novo mutations affecting two genes, PLXND1 and REV3L in MBS patients...
  11. Watanabe N, Mii S, Asai N, Asai M, Niimi K, Ushida K, et al. The REV7 subunit of DNA polymerase ? is essential for primordial germ cell maintenance in the mouse. J Biol Chem. 2013;288:10459-71 pubmed publisher
    ..5. These findings indicate that Rev7 is essential for PGC maintenance by prevention of apoptotic cell death in the mouse. ..
  12. Wojtaszek J, Lee C, D Souza S, Minesinger B, Kim H, D Andrea A, et al. Structural basis of Rev1-mediated assembly of a quaternary vertebrate translesion polymerase complex consisting of Rev1, heterodimeric polymerase (Pol) ?, and Pol ?. J Biol Chem. 2012;287:33836-46 pubmed
    ..a nucleotide opposite the lesion and with the heterodimeric B-family polymerase ?, consisting of the catalytic Rev3 subunit and the accessory Rev7 subunit, replacing the insertion polymerase to carry out primer extension past the ..
  13. Kajiwara K, Nagawawa H, Shimizu Nishikawa S, Ookuri T, Kimura M, Sugaya E. Molecular characterization of seizure-related genes isolated by differential screening. Biochem Biophys Res Commun. 1996;219:795-9 pubmed
    ..These data and our previous results suggest that intracellular calcium may play an important role for seizure-related pathophysiological changes in neuronal cells. ..
  14. Mekhail K, Khacho M, Carrigan A, Hache R, Gunaratnam L, Lee S. Regulation of ubiquitin ligase dynamics by the nucleolus. J Cell Biol. 2005;170:733-44 pubmed
    ..Data shown here provide the first evidence that cells have evolved a mechanism to regulate molecular networks by reversibly switching proteins between a mobile and static state. ..
  15. Lange S, Bedford E, Reh S, Wittschieben J, Carbajal S, Kusewitt D, et al. Dual role for mammalian DNA polymerase ? in maintaining genome stability and proliferative responses. Proc Natl Acad Sci U S A. 2013;110:E687-96 pubmed publisher
    ..Mice were produced in which Rev3L (the catalytic subunit of pol?) was deleted in tissues expressing keratin 5...
  16. Saribasak H, Maul R, Cao Z, Yang W, Schenten D, Kracker S, et al. DNA polymerase ? generates tandem mutations in immunoglobulin variable regions. J Exp Med. 2012;209:1075-81 pubmed publisher
    ..Additionally, data on tandem mutations from wild type, Pol?(+/-), Pol?(-/-), Ung(-/-), Msh2(-/-), Msh6(-/-), and Ung(-/-) Msh2(-/-) clones suggest that pol ? may function in the MSH2-MSH6 pathway. ..
  17. Wakana S, Sugaya E, Naramoto F, Yokote N, Maruyama C, Jin W, et al. Gene mapping of SEZ group genes and determination of pentylenetetrazol susceptible quantitative trait loci in the mouse chromosome. Brain Res. 2000;857:286-90 pubmed
    ..Since epilepsy is assumed to be a disease syndrome which is probably manifested by abnormal expression of multifocal genes, determination of the role of each chromosomal locus in the provocation of seizure activity is important. ..
  18. Lange S, Wittschieben J, Wood R. DNA polymerase zeta is required for proliferation of normal mammalian cells. Nucleic Acids Res. 2012;40:4473-82 pubmed publisher
    ..whether pol ? is necessary for proliferation of normal cells, primary mouse fibroblasts were established in which Rev3L could be conditionally inactivated by Cre recombinase...
  19. Kajiwara K, O Wang J, Sakurai T, Yamashita S, Tanaka M, Sato M, et al. Sez4 gene encoding an elongation subunit of DNA polymerase zeta is required for normal embryogenesis. Genes Cells. 2001;6:99-106 pubmed
    b>Sez4 identified as a seizure-activated gene shows a similarity to the yeast REV3 that encodes a catalytic subunit of the nonessential DNA polymerase zeta which is involved in error-prone translesion synthesis...
  20. Takeda K, Smyth M, Cretney E, Hayakawa Y, Kayagaki N, Yagita H, et al. Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development. J Exp Med. 2002;195:161-9 pubmed
    ..Moreover, development of spontaneous tumors in p53(+/-) mice was also promoted by neutralization of TRAIL. These results indicated a substantial role of TRAIL as an effector molecule that eliminates developing tumors. ..
  21. O Wang J, Kajiwara K, Kawamura K, Kimura M, Miyagishima H, Koseki H, et al. An essential role for REV3 in mammalian cell survival: absence of REV3 induces p53-independent embryonic death. Biochem Biophys Res Commun. 2002;293:1132-7 pubmed
    The REV3 gene of budding yeast encodes the catalytic subunit of DNA polymerase zeta that carries out translesion DNA synthesis...
  22. Enoiu M, Jiricny J, SCHARER O. Repair of cisplatin-induced DNA interstrand crosslinks by a replication-independent pathway involving transcription-coupled repair and translesion synthesis. Nucleic Acids Res. 2012;40:8953-64 pubmed publisher
    ..We conclude that transcription- and replication-dependent pathways contribute to cellular survival following treatment with crosslinking agents. ..
  23. Hashimoto K, Cho Y, Yang I, Akagi J, Ohashi E, Tateishi S, et al. The vital role of polymerase ? and REV1 in mutagenic, but not correct, DNA synthesis across benzo[a]pyrene-dG and recruitment of polymerase ? by REV1 to replication-stalled site. J Biol Chem. 2012;287:9613-22 pubmed publisher
    ..Knockout of the Rev1 gene decreased both the TLS efficiency and the miscoding frequency. Knockout of the Rev3L gene, coding for the catalytic subunit of pol ?, caused even greater decreases in these two TLS parameters; almost ..
  24. Van Sloun P, Varlet I, Sonneveld E, Boei J, Romeijn R, Eeken J, et al. Involvement of mouse Rev3 in tolerance of endogenous and exogenous DNA damage. Mol Cell Biol. 2002;22:2159-69 pubmed
    The Rev3 gene of Saccharomyces cerevisiae encodes the catalytic subunit of DNA polymerase zeta that is implicated in mutagenic translesion synthesis of damaged DNA...
  25. Fritzen R, Delbos F, De Smet A, Palancade B, Canman C, Aoufouchi S, et al. A single aspartate mutation in the conserved catalytic site of Rev3L generates a hypomorphic phenotype in vivo and in vitro. DNA Repair (Amst). 2016;46:37-46 pubmed publisher
    ..of yeast DNA polymerase ?, is required for UV resistance and UV-induced mutagenesis, while its mammalian ortholog, REV3L, plays further vital roles in cell proliferation and embryonic development...