title: DNA polymerase beta is the major dRP lyase involved in repair of oxidative base lesions in DNA by mammalian cell extracts.
abstract: 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.
authors.affiliation: MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Allinson
authors.forename: I I
authors.initials: II
authors.lastname: Dianova
authors.forename: G L
authors.initials: GL
authors.lastname: Dianov
mesh_terms: D000818:Animals; D001483:Base Sequence; D019757:Carbon-Oxygen Lyases / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D005347:Fibroblasts / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008190:Lyases / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010100:Oxygen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; C007419:dihydrouracil; C024829:8-hydroxyguanine; D014498:Uracil; D006147:Guanine; D004247:DNA; D019951:DNA Polymerase beta; D043223:Deoxyribonuclease IV (Phage T4-Induced); D008190:Lyases; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D010100:Oxygen