title: Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning.
abstract: For mammalian nucleotide excision repair (NER), DNA lesions are recognized in at least two steps involving detection of unpaired bases by the XPC protein complex and the subsequent verification of injured bases. Although lesion verification is important to ensure high damage discrimination and the accuracy of the repair system, it has been unclear how this is accomplished. Here, we show that damage verification involves scanning of a DNA strand from the site where XPC is initially bound. Translocation by the NER machinery exhibits a 5'-to-3' directionality, strongly suggesting involvement of the XPD helicase, a component of TFIIH. Furthermore, the initial orientation of XPC binding is crucial in that only one DNA strand is selected to search for the presence of lesions. Our results dissect the intricate molecular mechanism of NER and provide insights into a strategy for mammalian cells to survey large genomes to detect DNA damage.
authors: Biosignal Research Center, Kobe University, Rokkodai, Nada-ku, Hyogo, Japan. ksugasawa@garnet.kobe-u.ac.jp
authors: Kaoru
authors: K
authors: Sugasawa
authors: Jun-ichi
authors: J
authors: Akagi
authors: Ryotaro
authors: R
authors: Nishi
authors: Shigenori
authors: S
authors: Iwai
authors: Fumio
authors: F
authors: Hanaoka
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002460:Cell Line; D002474:Cell-Free System; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011740:Pyrimidine Dimers / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000378:metabolism; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D011740:Pyrimidine Dimers; D051758:Transcription Factor TFIIH; D004247:DNA; D000251:Adenosine Triphosphatases