Translesion synthesis by REV1

Stable Identifier
R-HSA-110312
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Pathway
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Homo sapiens
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REV1 (hREV1) encodes a template-dependent dCMP transferase that can insert a C residue opposite an abasic site (Lin et al. 1999, Gibbs et al. 2000). Interaction with monoubiquitinated PCNA at a DNA damage site enhances REV1-mediated translesion synthesis (TLS) (Garg and Burgers 2005, Wood et al. 2007). After REV1 incorporates dCMP opposite to the apurinic/apyrimidinic (AP) template site, TLS is continued by the DNA polymerase zeta complex (POLZ). POLZ consists of the catalytic subunit REV3L and the accessory subunit MAD2L2 (REV7). MAD2L2 binds REV1, thus recruiting POLZ to DNA damage site (Hara et al. 2010, Kikuchi et al. 2010, Xie et al. 1012). POLZ is error-prone and contributes to TLS-related mutagenesis (Shachar et al. 2009, Lee et al. 2014). POLZ has a low processivity and dissociates from the DNA template after incorporating less than 30 nucleotides (Nelson et al. 1996, Lee et al. 2014).

Literature References
PubMed ID Title Journal Year
23143872 Structural insights into the assembly of human translesion polymerase complexes

Xie, W, Yang, X, Xu, M, Jiang, T

Protein Cell 2012
17517887 A ubiquitin-binding motif in the translesion DNA polymerase Rev1 mediates its essential functional interaction with ubiquitinated proliferating cell nuclear antigen in response to DNA damage

Wood, A, Garg, P, Burgers, PM

J. Biol. Chem. 2007
16344468 Ubiquitinated proliferating cell nuclear antigen activates translesion DNA polymerases eta and REV1

Garg, P, Burgers, PM

Proc. Natl. Acad. Sci. U.S.A. 2005
8658138 Thymine-thymine dimer bypass by yeast DNA polymerase zeta

Nelson, JR, Lawrence, CW, Hinkle, DC

Science 1996
22859296 Structural basis of recruitment of DNA polymerase ? by interaction between REV1 and REV7 proteins

Kikuchi, S, Hara, K, Shimizu, T, Sato, M, Hashimoto, H

J. Biol. Chem. 2012
10536157 The human REV1 gene codes for a DNA template-dependent dCMP transferase.

Lin, W, Xin, H, Zhang, Y, Wu, X, Yuan, F

Nucleic Acids Res 1999
20164194 Crystal structure of human REV7 in complex with a human REV3 fragment and structural implication of the interaction between DNA polymerase zeta and REV1

Hara, K, Hashimoto, H, Murakumo, Y, Kobayashi, S, Kogame, T, Unzai, S, Akashi, S, Takeda, S, Shimizu, T, Sato, M

J. Biol. Chem. 2010
24449906 Human Pol ? purified with accessory subunits is active in translesion DNA synthesis and complements Pol ? in cisplatin bypass

Lee, YS, Gregory, MT, Yang, W

Proc. Natl. Acad. Sci. U.S.A. 2014
10760286 The function of the human homolog of Saccharomyces cerevisiae REV1 is required for mutagenesis induced by UV light.

Gibbs, PE, Wang, XD, Li, Z, McManus, TP, McGregor, WG, Lawrence, CW, Maher, VM

Proc Natl Acad Sci U S A 2000
19153606 Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals

Shachar, S, Ziv, O, Avkin, S, Adar, S, Wittschieben, J, Reissner, T, Chaney, S, Friedberg, EC, Wang, Z, Carell, T, Geacintov, N, Livneh, Z

EMBO J. 2009
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