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Structural basis of pyrimidine-pyrimidone (6-4) photoproduct recognition by UV-DDB in the nucleosome.

  • Osakabe A Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
  • Tachiwana H Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
  • Kagawa W 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.
  • Horikoshi N Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
  • Matsumoto S Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe-shi, Hyogo 657-8501, Japan.
  • Hasegawa M Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka-shi, Osaka 560-8531, Japan.
  • Matsumoto N Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka-shi, Osaka 560-8531, Japan.
  • Toga T Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka-shi, Osaka 560-8531, Japan.
  • Yamamoto J Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka-shi, Osaka 560-8531, Japan.
  • Hanaoka F Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
  • Thomä NH Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH 4058 Basel, Switzerland.
  • Sugasawa K Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe-shi, Hyogo 657-8501, Japan.
  • Iwai S Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka-shi, Osaka 560-8531, Japan.
  • Kurumizaka H Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
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  • 2015-11-18
Published in:
  • Scientific reports. - 2015
Crystallography, X-Ray
DNA
DNA-Binding Proteins
Electrophoretic Mobility Shift Assay
Histones
Humans
Maleimides
Mutagenesis, Site-Directed
Nucleic Acid Conformation
Nucleosomes
Protein Binding
Pyrimidine Dimers
Recombinant Fusion Proteins
Ultraviolet Rays
English UV-DDB, an initiation factor for the nucleotide excision repair pathway, recognizes 6-4PP lesions through a base flipping mechanism. As genomic DNA is almost entirely accommodated within nucleosomes, the flipping of the 6-4PP bases is supposed to be extremely difficult if the lesion occurs in a nucleosome, especially on the strand directly contacting the histone surface. Here we report that UV-DDB binds efficiently to nucleosomal 6-4PPs that are rotationally positioned on the solvent accessible or occluded surface. We determined the crystal structures of nucleosomes containing 6-4PPs in these rotational positions, and found that the 6-4PP DNA regions were flexibly disordered, especially in the strand exposed to the solvent. This characteristic of 6-4PP may facilitate UV-DDB binding to the damaged nucleosome. We present the first atomic-resolution pictures of the detrimental DNA cross-links of neighboring pyrimidine bases within the nucleosome, and provide the mechanistic framework for lesion recognition by UV-DDB in chromatin.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://susi.usi.ch/global/documents/273255
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