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5-Hydroxyuracil (5-OHU) in DNA, arising during endogenous DNA damage and caused by ionizing radiation, is removed by the base excision repair pathway. However, in addition to base lesions, ionizing radiation also generates DNA single-strand breaks (SSBs). When these DNA lesions are located in the proximity of each other, this may result in a profound effect on both repair of the damaged base and the SSB. We therefore examined the repair of DNA substrates containing 5-OHU lesions in the proximity of the 3'-end of a SSB. We found that SSB repair by DNA ligase IIIalpha and DNA polymerase beta is impaired by the presence of the nearby 5-OHU lesion, indicating the requirement for a DNA glycosylase which would be able to remove 5-OHU before SSB repair. Subsequently, we found that although both SMUG1 and NEIL1 are able to excise 5-OHU lesions located in the proximity of the 3'-end of a DNA SSB, NEIL1 is more efficient in the repair of these DNA lesions.

Original publication

DOI

10.1021/bi0622569

Type

Journal article

Journal

Biochemistry

Publication Date

03/04/2007

Volume

46

Pages

4158 - 4163

Keywords

DNA Damage, DNA Glycosylases, DNA Ligase ATP, DNA Ligases, DNA Polymerase beta, DNA Repair, Humans, Poly-ADP-Ribose Binding Proteins, Uracil, Uracil-DNA Glycosidase, Xenopus Proteins