Article
- The EMBO Journal (2004) 23, 4484 - 4494
- doi:10.1038/sj.emboj.7600424
Published online: 21 October 2004
Subject Categories:
High-efficiency bypass of DNA damage by human DNA polymerase Q
Mineaki Seki1, Chikahide Masutani2, Lee Wei Yang3, Anthony Schuffert1, Shigenori Iwai4, Ivet Bahar3 and Richard D Wood1
- University of Pittsburgh Cancer Institute, Hillman Cancer Center, Research Pavilion, Pittsburgh, PA, USA
- Graduate School of Frontier Biosciences, Osaka University and CREST, Japan Science and Technology Corporation, Suita, Osaka, Japan
- Department of Molecular Genetics & Biochemistry, Center for Computational Biology and Bioinformatics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka, Japan
Correspondence to:
Richard D Wood, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213, USA. Tel.: +1 412 623 7762; Fax: +1 412 623 7761; E-mail: rdwood@pitt.edu
Received 17 June 2004; Accepted 27 August 2004
Abstract
Endogenous DNA damage arises frequently, particularly apurinic (AP) sites. These must be dealt with by cells in order to avoid genotoxic effects. DNA polymerase 
is a newly identified enzyme encoded by the human POLQ gene. We find that POLQ has an exceptional ability to bypass an AP site, inserting A with 22% of the efficiency of a normal template, and continuing extension as avidly as with a normally paired base. POLQ preferentially incorporates A opposite an AP site and strongly disfavors C. On nondamaged templates, POLQ makes frequent errors, incorporating G or T opposite T about 1% of the time. This very low fidelity distinguishes POLQ from other A-family polymerases. POLQ has three sequence insertions between conserved motifs in its catalytic site. One insert of 
22 residues into the tip of the polymerase thumb subdomain is predicted to confer considerable flexibility and additional DNA contacts to affect enzyme fidelity. POLQ is the only known enzyme that efficiently carries out both the insertion and extension steps for bypass of AP sites, commonly formed as endogenous genomic lesions.
Keywords:
- AP site,
- DNA damage,
- DNA polymerase,
- POLQ,
- thymine glycol
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