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The repair of oxidative base lesions in DNA is a coordinated chain of reactions that includes removal of the damaged base, incision of the phosphodiester backbone at the abasic sugar residue, incorporation of an undamaged nucleotide and sealing of the DNA strand break. Although removal of a damaged base in mammalian cells is initiated primarily by a damage-specific DNA glycosylase, several lyases and DNA polymerases may contribute to the later stages of repair. DNA polymerase beta (Pol beta) was implicated recently as the major polymerase involved in repair of oxidative base lesions; however, the identity of the lyase participating in the repair of oxidative lesions is unclear. We studied the mechanism by which mammalian cell extracts process DNA substrates containing a single 8-oxoguanine or 5,6-dihydrouracil at a defined position. We find that, when repair synthesis proceeds through a Pol beta-dependent single nucleotide replacement mechanism, the 5'-deoxyribosephosphate lyase activity of Pol beta is essential for repair of both lesions.

Original publication

DOI

10.1093/emboj/20.23.6919

Type

Journal article

Journal

EMBO J

Publication Date

03/12/2001

Volume

20

Pages

6919 - 6926

Keywords

Animals, Base Sequence, Carbon-Oxygen Lyases, Cell Line, DNA, DNA Damage, DNA Polymerase beta, DNA Repair, DNA-(Apurinic or Apyrimidinic Site) Lyase, Deoxyribonuclease IV (Phage T4-Induced), Fibroblasts, Guanine, Humans, Lyases, Mice, Mice, Knockout, Models, Genetic, Molecular Sequence Data, Mutation, Oxygen, Recombinant Proteins, Time Factors, Uracil