POLK incorporates dNMP opposite to damaged DNA base

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
Participant Of
Catalyst Activity
Catalyst Activity
DNA-directed DNA polymerase activity of POLK:REV1:POLZ:MonoUb:K164-PCNA:RPA:RFC:Tg-DNA Template,OGUA-DNA Template,BPDE-G-DNA Template [nucleoplasm]
Physical Entity
Orthologous Events
Cite Us!