Crystal structure of the nucleosome containing ultraviolet light-induced cyclobutane pyrimidine dimer

Naoki Horikoshi, Hiroaki Tachiwana, Wataru Kagawa, Akihisa Osakabe, Syota Matsumoto, Shigenori Iwai, Kaoru Sugasawa, Hitoshi Kurumizaka

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)117-122
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume471
Issue number1
DOIs
Publication statusPublished - 2016 Feb 26

Fingerprint

Pyrimidine Dimers
Nucleosomes
Ultraviolet Rays
Crystal structure
DNA Repair
Repair
Nucleotides
Mammals
Thymine
DNA
Adenine
Chromatin
Hydrogen
Hydrogen bonds

Keywords

  • Chromatin
  • Cyclobutane pyrimidine dimer
  • Nucleosome
  • Nucleotide excision repair
  • UV-DDB

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Crystal structure of the nucleosome containing ultraviolet light-induced cyclobutane pyrimidine dimer. / Horikoshi, Naoki; Tachiwana, Hiroaki; Kagawa, Wataru; Osakabe, Akihisa; Matsumoto, Syota; Iwai, Shigenori; Sugasawa, Kaoru; Kurumizaka, Hitoshi.

In: Biochemical and Biophysical Research Communications, Vol. 471, No. 1, 26.02.2016, p. 117-122.

Research output: Contribution to journalArticle

Horikoshi, N, Tachiwana, H, Kagawa, W, Osakabe, A, Matsumoto, S, Iwai, S, Sugasawa, K & Kurumizaka, H 2016, 'Crystal structure of the nucleosome containing ultraviolet light-induced cyclobutane pyrimidine dimer', Biochemical and Biophysical Research Communications, vol. 471, no. 1, pp. 117-122. https://doi.org/10.1016/j.bbrc.2016.01.170
Horikoshi, Naoki ; Tachiwana, Hiroaki ; Kagawa, Wataru ; Osakabe, Akihisa ; Matsumoto, Syota ; Iwai, Shigenori ; Sugasawa, Kaoru ; Kurumizaka, Hitoshi. / Crystal structure of the nucleosome containing ultraviolet light-induced cyclobutane pyrimidine dimer. In: Biochemical and Biophysical Research Communications. 2016 ; Vol. 471, No. 1. pp. 117-122.
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AU - Iwai, Shigenori

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AB - 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.

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