title: Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase.
abstract: The XPC-HR23B complex recognizes various helix-distorting lesions in DNA and initiates global genome nucleotide excision repair. Here we describe a novel functional interaction between XPC-HR23B and thymine DNA glycosylase (TDG), which initiates base excision repair (BER) of G/T mismatches generated by spontaneous deamination of 5-methylcytosine. XPC-HR23B stimulated TDG activity by promoting the release of TDG from abasic sites that result from the excision of mismatched T bases. In the presence of AP endonuclease (APE), XPC-HR23B had an additive effect on the enzymatic turnover of TDG without significantly inhibiting the subsequent action of APE. Our observations suggest that XPC-HR23B may participate in BER of G/T mismatches, thereby contributing to the suppression of spontaneous mutations that may be one of the contributory factors for the promotion of carcinogenesis in xeroderma pigmentosum genetic complementation group C patients.
authors.affiliation: Cellular Physiology Laboratory, Discovery Research Institute, RIKEN, Japan Science and Technology Corporation, Wako, Saitama.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Shigenori
authors.initials: S
authors.lastname: Iwai
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
mesh_terms: D001483:Base Sequence; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015183:Restriction Mapping; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C086984:XPC protein, human; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer)