POLK incorporates dNMP opposite to damaged DNA base

Stable Identifier
Reaction [transition]
Homo sapiens
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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

Prakash, L, Roy Choudhury, J, Yoon, JH, Park, J, Prakash, S

J. Biol. Chem. 2014
19492058 Structure of human DNA polymerase kappa inserting dATP opposite an 8-OxoG DNA lesion

Johnson, RE, Vasquez-Del Carpio, R, Prakash, L, Aggarwal, AK, Lone, S, Silverstein, TD, Swan, MK, Choudhury, JR, Prakash, S

PLoS ONE 2009
22721435 Replication of the 2,6-diamino-4-hydroxy-N(5)-(methyl)-formamidopyrimidine (MeFapy-dGuo) adduct by eukaryotic DNA polymerases

Rizzo, CJ, Christov, PP, Lloyd, RS, Wood, RD, Takata, K, Choi, JY, Guengerich, FP, Yamanaka, K

Chem. Res. Toxicol. 2012
20660785 Error-free replicative bypass of thymine glycol by the combined action of DNA polymerases kappa and zeta in human cells

Prakash, L, Yoon, JH, Bhatia, G, Prakash, S

Proc. Natl. Acad. Sci. U.S.A. 2010
12952891 Human DNA polymerase kappa uses template-primer misalignment as a novel means for extending mispaired termini and for generating single-base deletions

Washington, MT, Prakash, L, Wolfle, WT, Prakash, S

Genes Dev. 2003
10887153 Error-prone bypass of certain DNA lesions by the human DNA polymerase kappa

Kusumoto, R, Iwai, S, Masutani, C, Ohashi, E, Ogi, T, Ohmori, H, Hanaoka, F

Genes Dev. 2000
12145297 Human DNA polymerase kappa bypasses and extends beyond thymine glycols during translesion synthesis in vitro, preferentially incorporating correct nucleotides

Hatahet, Z, Friedberg, EC, Gerlach, VL, Fischhaber, PL, Feaver, WJ, Wallace, SS

J. Biol. Chem. 2002
3941892 Detection of smoking-related covalent DNA adducts in human placenta

Randerath, K, Everson, RB, Cefalo, RC, Santella, RM, Avitts, TA, Randerath, E

Science 1986
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, Friedberg, EC, Velasco-Miguel, S, Geacintov, N, Livneh, Z, Goldsmith, M

J. Biol. Chem. 2004
11058110 Error-free and error-prone lesion bypass by human DNA polymerase kappa in vitro

Geacintov, NE, Zhang, Y, Yuan, F, Wang, M, Taylor, JS, Wang, Z, Rechkoblit, O, Wu, X

Nucleic Acids Res. 2000
22772988 Preferred WMSA catalytic mechanism of the nucleotidyl transfer reaction in human DNA polymerase ? elucidates error-free bypass of a bulky DNA lesion

Broyde, S, Wang, L, Geacintov, NE, Zhang, Y, Wang, S, Lior-Hoffmann, L

Nucleic Acids Res. 2012
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]

Orthologous Events
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