Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 471, Issue 1, Pages 117-122Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.01.170
Keywords
Cyclobutane pyrimidine dimer; Nucleosome; Chromatin; Nucleotide excision repair; UV-DDB
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Funding
- MEXT KAKENHI Grants [25116002, 26116521]
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
- Japan Agency for Medical Research and Development (AMED)
- Waseda Research Institute for Science and Engineering
- Platform Project for Supporting Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science)
- Grants-in-Aid for Scientific Research [26116521, 25116002, 26840025] Funding Source: KAKEN
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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 angstrom 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. (C) 2016 Elsevier Inc. All rights reserved.
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