title: Roles of base excision repair subpathways in correcting oxidized abasic sites in DNA.
abstract: Base excision DNA repair (BER) is fundamentally important in handling diverse lesions produced as a result of the intrinsic instability of DNA or by various endogenous and exogenous reactive species. Defects in the BER process have been associated with cancer susceptibility and neurodegenerative disorders. BER funnels diverse base lesions into a common intermediate, apurinic/apyrimidinic (AP) sites. The repair of AP sites is initiated by the major human AP endonuclease, Ape1, or by AP lyase activities associated with some DNA glycosylases. Subsequent steps follow either of two distinct BER subpathways distinguished by repair DNA synthesis of either a single nucleotide (short-patch BER) or multiple nucleotides (long-patch BER). As the major repair mode for regular AP sites, the short-patch BER pathway removes the incised AP lesion, a 5'-deoxyribose-5-phosphate moiety, and replaces a single nucleotide using DNA polymerase (Polbeta). However, short-patch BER may have difficulty handling some types of lesions, as shown for the C1'-oxidized abasic residue, 2-deoxyribonolactone (dL). Recent work indicates that dL is processed efficiently by Ape1, but that short-patch BER is derailed by the formation of stable covalent crosslinks between Ape1-incised dL and Polbeta. The long-patch BER subpathway effectively removes dL and thereby prevents the formation of DNA-protein crosslinks. In coping with dL, the cellular choice of BER subpathway may either completely repair the lesion, or complicate the repair process by forming a protein-DNA crosslink.
authors.affiliation: Department of Life Science, Dongguk University, Seoul, South Korea.
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Sung
authors.forename: Bruce
authors.initials: B
authors.lastname: Demple
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D019951:DNA Polymerase beta / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology*; D006801:Humans; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D004247:DNA; D019951:DNA Polymerase beta