title: Crystal structure of the nucleosome containing ultraviolet light-induced cyclobutane pyrimidine dimer.
abstract: The cyclobutane pyrimidine dimer (CPD) is induced in genomic DNA by ultraviolet (UV) light. In mammals, this photolesion is primarily induced within nucleosomal DNA, and repaired exclusively by the nucleotide excision repair (NER) pathway. However, the mechanism by which the CPD is accommodated within the nucleosome has remained unknown. We now report the crystal structure of a nucleosome containing CPDs. In the nucleosome, the CPD induces only limited local backbone distortion, and the affected bases are accommodated within the duplex. Interestingly, one of the affected thymine bases is located within 3.0 Å from the undamaged complementary adenine base, suggesting the formation of complementary hydrogen bonds in the nucleosome. We also found that UV-DDB, which binds the CPD at the initial stage of the NER pathway, also efficiently binds to the nucleosomal CPD. These results provide important structural and biochemical information for understanding how the CPD is accommodated and recognized in chromatin.
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan; Research Institute for Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Horikoshi
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tachiwana
authors.affiliation: Department of Interdisciplinary Science and Engineering, Program in Chemistry and Life Science, School of Science and Engineering, Meisei University, 2-1-1 Hodokubo, Hino-shi, Tokyo 191-8506, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kagawa
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Osakabe
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe-shi, Hyogo 657-8501, Japan.
authors.forename: Syota
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka-shi, Osaka 560-8531, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Iwai
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe-shi, Hyogo 657-8501, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan; Research Institute for Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan; Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. Electronic address: kurumizaka@waseda.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000528:radiation effects / Q000648:ultrastructure*; D006860:Hydrogen Bonding; D008968:Molecular Conformation / Q000528:radiation effects; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000528:radiation effects* / Q000648:ultrastructure*; D011485:Protein Binding; D011740:Pyrimidine Dimers / Q000737:chemistry* / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D009707:Nucleosomes; D011740:Pyrimidine Dimers; D004247:DNA
keywords: Chromatin; Cyclobutane pyrimidine dimer; Nucleosome; Nucleotide excision repair; UV-DDB