NEIL1 is the major DNA glycosylase that processes 5-hydroxyuracil in the proximity of a DNA single-strand break.
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.
Parsons
Jason L
JL
MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, UK.
Kavli
Bodil
B
Slupphaug
Geir
G
Dianov
Grigory L
GL
D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology*; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D014498:Uracil / Q000031:analogs & derivatives* / Q000378:metabolism; D051981:Uracil-DNA Glycosidase / Q000378:metabolism; D029867:Xenopus Proteins
D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; C045975:5-hydroxyuracil; D014498:Uracil; D019951:DNA Polymerase beta; C492570:CCNO protein, human; D045647:DNA Glycosylases; C473634:NEIL1 protein, human; C498095:SMUG1 protein, human; D051981:Uracil-DNA Glycosidase; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus