Nucleic Acids Research Advance Access originally published online on January 30, 2007
Nucleic Acids Research 2007 35(4):1054-1063; doi:10.1093/nar/gkl1115
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Nucleic Acids Research, 2007, Vol. 35, No. 4 1054-1063
© 2007 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nucleic Acid Enzymes |
DNA polymerase 
-dependent repair of DNA single strand breaks containing 3'-end proximal lesions
1MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire, UK, 2Department of Pathology, University of Washington, Seattle, Washington 98195, USA and 3Department of Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA
*To whom correspondence should be addressed. Tel: (44) 1235 841 134; Fax: (44) 1235 841 200; E-mail: g.dianov{at}har.mrc.ac.uk
Received October 6, 2006. Revised November 30, 2006. Accepted December 6, 2006.
Base excision repair (BER) is the major pathway for the repair of simple, non-bulky lesions in DNA that is initiated by a damage-specific DNA glycosylase. Several human DNA glycosylases exist that efficiently excise numerous types of lesions, although the close proximity of a single strand break (SSB) to a DNA adduct can have a profound effect on both BER and SSB repair. We recently reported that DNA lesions located as a second nucleotide 5'-upstream to a DNA SSB are resistant to DNA glycosylase activity and this study further examines the processing of these ‘complex’ lesions. We first demonstrated that the damaged base should be excised before SSB repair can occur, since it impaired processing of the SSB by the BER enzymes, DNA ligase III
and DNA polymerase ß. Using human whole cell extracts, we next isolated the major activity against DNA lesions located as a second nucleotide 5'-upstream to a DNA SSB and identified it as DNA polymerase 
(Pol ). Using recombinant protein we confirmed that the 3'-5'-exonuclease activity of Pol can efficiently remove these DNA lesions. Furthermore, we demonstrated that mouse embryonic fibroblasts, deficient in the exonuclease activity of Pol are partially deficient in the repair of these ‘complex’ lesions, demonstrating the importance of Pol during the repair of DNA lesions in close proximity to a DNA SSB, typical of those induced by ionizing radiation.
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