title: Delay of gap filling during nucleotide excision repair by base excision repair: the concept of competition exemplified by the effect of propolis.
abstract: Nucleotide excision repair (NER) consists of a sequence of events including DNA damage recognition, excision of the damage containing oligonucleotide, gap filling, and ligation. We found that gap filling during the repair of ultraviolet (UV)C-induced DNA lesions was inhibited by various compounds, e.g., amoxicillin, and mixtures, e.g., propolis, the materials that could induce oxidative DNA damage in serum-supplemented cell cultures. Such inhibitory effect was also demonstrated by the immunostaining experiment and host cell reactivation assay. In this study, we link the repair of oxidative DNA damage with the inhibition of gap filling. Our experimental evidence includes the following: (1) induction of oxidative DNA damage and inhibition of gap filling were quantitatively correlated; (2) although the repair of UV-induced DNA damage was delayed in the presence of propolis, the repair of propolis-induced oxidative DNA damage proceeded regardless of preexposure to UV radiation; (3) inhibition of gap filling by propolis was absent in base excision repair (BER)-deficient cells; (4) suppression of propolis-induced oxidative DNA damage by β-carotene abolished the inhibition of gap filling; and (5) inhibition of gap filling was also found with typical BER-inducing agents such as hydrogen peroxide, menadione, and methyl methanesulfonate. We propose that competition may occur between NER and BER, which results in delay of gap filling. Our study reveals the dominancy of BER over NER.
authors.affiliation: Institute of Molecular Medicine, National Tsing-Hua University, Hsinchu 30013, Taiwan.
authors.forename: Mei-Kuang
authors.initials: MK
authors.lastname: Chen
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Tsai
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Li
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Liou
authors.forename: Ezhilan Sathyapriya
authors.initials: ES
authors.lastname: Taniga
authors.forename: Dai-Wei
authors.initials: DW
authors.lastname: Chang
authors.forename: Toshio
authors.initials: T
authors.lastname: Mori
authors.forename: Yin-Chang
authors.initials: YC
authors.lastname: Liu
mesh_terms: D001973:Bromodeoxyuridine / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008741:Methyl Methanesulfonate / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011429:Propolis / Q000633:toxicity*; D014466:Ultraviolet Rays; D024483:Vitamin K 3 / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D019207:beta Carotene; D024483:Vitamin K 3; D004247:DNA; D011429:Propolis; D008741:Methyl Methanesulfonate; D006861:Hydrogen Peroxide; D001973:Bromodeoxyuridine