Reactome | POLZ extends translesion synthesis

POLZ extends translesion synthesis

Stable Identifier

R-HSA-110311

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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
21143968	The role of hRev7, the accessory subunit of hPol?, in translesion synthesis past DNA damage induced by benzo[a]pyrene diol epoxide (BPDE) McCormick, JJ, Neal, JA, Maher, VM, Fletcher, KL	BMC Cell Biol.	2010
8751446	Deoxycytidyl transferase activity of yeast REV1 protein Nelson, JR, Hinkle, DC, Lawrence, CW	Nature	1996
8658138	Thymine-thymine dimer bypass by yeast DNA polymerase zeta Nelson, JR, Hinkle, DC, Lawrence, CW	Science	1996
24449906	Human Pol ? purified with accessory subunits is active in translesion DNA synthesis and complements Pol ? in cisplatin bypass Gregory, MT, Yang, W, Lee, YS	Proc. Natl. Acad. Sci. U.S.A.	2014
19153606	Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals Avkin, S, Chaney, S, Shachar, S, Adar, S, Reissner, T, Carell, T, Friedberg, EC, Wang, Z, Geacintov, N, Wittschieben, J, Ziv, O, Livneh, Z	EMBO J.	2009