Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Aug 1;24(15):2805.
doi: 10.3390/molecules24152805.

Mammalian DNA Polymerase Kappa Activity and Specificity

Hannah R Stern  1 , Jana Sefcikova  1 , Victoria E Chaparro  1 , Penny J Beuning  2
Affiliations
Review

Mammalian DNA Polymerase Kappa Activity and Specificity

Hannah R Stern et al. Molecules. .

Abstract

DNA polymerase (pol) kappa is a Y-family translesion DNA polymerase conserved throughout all domains of life. Pol kappa is special6 ized for the ability to copy DNA containing minor groove DNA adducts, especially N2-dG adducts, as well as to extend primer termini containing DNA damage or mismatched base pairs. Pol kappa generally cannot copy DNA containing major groove modifications or UV-induced photoproducts. Pol kappa can also copy structured or non-B-form DNA, such as microsatellite DNA, common fragile sites, and DNA containing G quadruplexes. Thus, pol kappa has roles both in maintaining and compromising genomic integrity. The expression of pol kappa is altered in several different cancer types, which can lead to genome instability. In addition, many cancer-associated single-nucleotide polymorphisms have been reported in the POLK gene, some of which are associated with poor survival and altered chemotherapy response. Because of this, identifying inhibitors of pol kappa is an active area of research. This review will address these activities of pol kappa, with a focus on lesion bypass and cellular mutagenesis.

Keywords: DNA damage; DNA replication; Y-family; chemotherapy resistance; primer extension; translesion DNA synthesis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
(a) Primer extension by translesion synthesis showing both the insertion and extension steps. The dot indicates the site of a lesion. (b) Direct extension (top) versus a one-nucleotide deletion resulting from looping a template base out of the DNA helix.
Figure 2
Figure 2
(a) Diagram of the domains of human pol κ: In addition to the polymerase domains, PCNA-interacting peptide (PIP) regions, Rev1-interacting region (RIR), and ubiquitin-binding zinc finger (UBZ) domains are shown. (b) The structure of the polymerase domain of human pol κ with domains colored as in Figure 2a (PDB ID: 6CST) [23]. (c) Close-up view of the structure of pol κ highlighting the active site residues in contact with the incoming nucleotide. The catalytic residues D107, D198, and E199 are shown in yellow sticks with red oxygen atoms; others are shown as sticks colored by the domain as in Figure 2a,b. Metal ions are shown as green spheres.
Figure 3
Figure 3
Structures of undamaged dG and dA and examples of damaged DNA bases.
See this image and copyright information in PMC

References

    1. Sale J.E., Lehmann A.R., Woodgate R. Y-family DNA polymerases and their role in tolerance of cellular DNA damage. Nat. Rev. Mol. Cell. Biol. 2012;13:141–152. doi: 10.1038/nrm3289. - DOI - PMC - PubMed
    1. Goodman M.F., Woodgate R. Translesion DNA polymerases. Cold Spring Harb Perspect Biol. 2013;5:a010363. doi: 10.1101/cshperspect.a010363. - DOI - PMC - PubMed
    1. Ling H., Boudsocq F., Woodgate R., Yang W. Crystal Structure of a Y-Family DNA Polymerase in Action: A Mechanism for Error-Prone and Lesion-Bypass Replication. Cell. 2001;107:91–102. doi: 10.1016/S0092-8674(01)00515-3. - DOI - PubMed
    1. Vaisman A., Woodgate R. Translesion DNA polymerases in eukaryotes: What makes them tick? Crit. Rev. Biochem. Mol. Biol. 2017;52:274–303. doi: 10.1080/10409238.2017.1291576. - DOI - PMC - PubMed
    1. Gruz P., Pisani F.M., Shimizu M., Yamada M., Hayashi I., Morikawa K., Nohmi T. Synthetic activity of Sso DNA polymerase Y1, an archaeal DinB-like DNA polymerase, is stimulated by processivity factors proliferating cell nuclear antigen and replication factor C. J. Biol. Chem. 2001;276:47394–47401. doi: 10.1074/jbc.M107213200. - DOI - PubMed

LinkOut - more resources