POLZ extends translesion synthesis

Stable Identifier
R-HSA-110311
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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After REV1 inserts a nucleotide directly opposite the template lesion, translesion synthesis (TLS) is continued by DNA polymerase zeta (POLZ), a complex of REV3L and MAD2L2 (REV3 and REV7 in yeast) (Nelson et al. 1996a, Neal et al. 2010). POLZ is a poorly processive enzyme in both yeast and humans and usually incorporates less than 30 nucleotides before it dissociates from the template. In human cells, the processivity of POLZ is increased in the presence of DNA polymerase delta (POLD) subunits POLD2 and POLD3, which act as accessory subunits for POLZ (Nelson et al. 1996b, Lee et al. 2014). POLZ is error-prone, especially in the context of TLS across AP (apurinic/apyrimidinic) sites, resulting in incorporation of mispaired dNTPs, which contributes to TLS-related mutagenesis (Shachar et al. 2009, Lee et al. 2014).

Literature References
PubMed ID Title Journal Year
8751446 Deoxycytidyl transferase activity of yeast REV1 protein

Nelson, JR, Lawrence, CW, Hinkle, DC

Nature 1996
21143968 The role of hRev7, the accessory subunit of hPol?, in translesion synthesis past DNA damage induced by benzo[a]pyrene diol epoxide (BPDE)

Neal, JA, Fletcher, KL, McCormick, JJ, Maher, VM

BMC Cell Biol. 2010
8658138 Thymine-thymine dimer bypass by yeast DNA polymerase zeta

Nelson, JR, Lawrence, CW, Hinkle, DC

Science 1996
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
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
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
DNA-directed DNA polymerase activity of POLZ:REV1:MonoUb:K164-PCNA:RPA:RFC:(AP:Cyt)-DNA Template [nucleoplasm]
Physical Entity
Activity
Orthologous Events
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Created