Reactome | POLK incorporates dNMP opposite to damaged DNA base

POLK incorporates dNMP opposite to damaged DNA base

Stable Identifier

R-HSA-5655892

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

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POLK incorporates dNMP opposite to damaged DNA base

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DNA polymerase kappa (POLK) is the most efficient in incorporation of nucleotides opposite to oxidation derivatives of DNA bases, such as thymine glycol (Tg) and 8-oxoguanine (OGUA). POLK preferentially incorporates dAMP opposite both Tg and OGUA, resulting in error-free translesion DNA synthesis (TLS) across Tg lesions (Fischhaber et al. 2002, Yoon et al. 2010, Yoon et al. 2014) and frequent G:C -> T:A transversions at OGUA lesions (Zhang et al. 2000, Vasquez-Del Carpio et al. 2009). POLK is also efficient in TLS across bulky DNA adducts, such as the smoking-related benzo(a)pyrene diol epoxide guanine adduct (BPDE-G) (Everson et al. 1986), and it correctly incorporates dCMP opposite to BPDE-G (Zhang et al. 2000, Avkin et al. 2004, Lior-Hoffmann et al. 2012, Christov et al. 2012). POLK is incapable of TLS across thymine-thymine dimers (Ohashi et al. 2000) and shows a very low efficiency in TLS across AP sites, where it mainly causes single base deletions (-1 frameshifts) through template-primer misalignment (Ohashi et al. 2000, Wolfle et al. 2003).

Literature References

PubMed ID	Title	Journal	Year
24648516	A role for DNA polymerase ? in promoting replication through oxidative DNA lesion, thymine glycol, in human cells Yoon, JH, Roy Choudhury, J, Park, J, Prakash, S, Prakash, L	J. Biol. Chem.	2014
12952891	Human DNA polymerase kappa uses template-primer misalignment as a novel means for extending mispaired termini and for generating single-base deletions Wolfle, WT, Washington, MT, Prakash, L, Prakash, S	Genes Dev.	2003
11058110	Error-free and error-prone lesion bypass by human DNA polymerase kappa in vitro Zhang, Y, Yuan, F, Wu, X, Wang, M, Rechkoblit, O, Taylor, JS, Geacintov, NE, Wang, Z	Nucleic Acids Res.	2000
12145297	Human DNA polymerase kappa bypasses and extends beyond thymine glycols during translesion synthesis in vitro, preferentially incorporating correct nucleotides Fischhaber, PL, Gerlach, VL, Feaver, WJ, Hatahet, Z, Wallace, SS, Friedberg, EC	J. Biol. Chem.	2002
22721435	Replication of the 2,6-diamino-4-hydroxy-N(5)-(methyl)-formamidopyrimidine (MeFapy-dGuo) adduct by eukaryotic DNA polymerases Christov, PP, Yamanaka, K, Choi, JY, Takata, K, Wood, RD, Guengerich, FP, Lloyd, RS, Rizzo, CJ	Chem. Res. Toxicol.	2012
19492058	Structure of human DNA polymerase kappa inserting dATP opposite an 8-OxoG DNA lesion Vasquez-Del Carpio, R, Silverstein, TD, Lone, S, Swan, MK, Choudhury, JR, Johnson, RE, Prakash, S, Prakash, L, Aggarwal, AK	PLoS ONE	2009
3941892	Detection of smoking-related covalent DNA adducts in human placenta Everson, RB, Randerath, E, Santella, RM, Cefalo, RC, Avitts, TA, Randerath, K	Science	1986
20660785	Error-free replicative bypass of thymine glycol by the combined action of DNA polymerases kappa and zeta in human cells Yoon, JH, Bhatia, G, Prakash, S, Prakash, L	Proc. Natl. Acad. Sci. U.S.A.	2010
10887153	Error-prone bypass of certain DNA lesions by the human DNA polymerase kappa Ohashi, E, Ogi, T, Kusumoto, R, Iwai, S, Masutani, C, Hanaoka, F, Ohmori, H	Genes Dev.	2000
22772988	Preferred WMSA catalytic mechanism of the nucleotidyl transfer reaction in human DNA polymerase ? elucidates error-free bypass of a bulky DNA lesion Lior-Hoffmann, L, Wang, L, Wang, S, Geacintov, NE, Broyde, S, Zhang, Y	Nucleic Acids Res.	2012
15475561	Quantitative analysis of translesion DNA synthesis across a benzo[a]pyrene-guanine adduct in mammalian cells: the role of DNA polymerase kappa Avkin, S, Goldsmith, M, Velasco-Miguel, S, Geacintov, N, Friedberg, EC, Livneh, Z	J. Biol. Chem.	2004