Structural basis of pyrimidine-pyrimidone (6–4) photoproduct recognition by UV-DDB in the nucleosome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-11-17

AUTHORS

Akihisa Osakabe, Hiroaki Tachiwana, Wataru Kagawa, Naoki Horikoshi, Syota Matsumoto, Mayu Hasegawa, Naoyuki Matsumoto, Tatsuya Toga, Junpei Yamamoto, Fumio Hanaoka, Nicolas H. Thomä, Kaoru Sugasawa, Shigenori Iwai, Hitoshi Kurumizaka

ABSTRACT

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. More... »

PAGES

16330

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep16330

DOI

http://dx.doi.org/10.1038/srep16330

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022470883

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26573481


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41 detrimental DNA
42 excision repair pathway
43 factors
44 first atomic-resolution pictures
45 flipping
46 flipping mechanism
47 framework
48 genomic DNA
49 histone surface
50 initiation factors
51 lesion recognition
52 lesions
53 mechanism
54 mechanistic framework
55 nucleosomes
56 nucleotide excision repair pathway
57 pathway
58 photoproduct recognition
59 picture
60 position
61 pyrimidine bases
62 pyrimidine-pyrimidone (6–4) photoproduct recognition
63 recognition
64 region
65 repair pathways
66 rotational position
67 solvent
68 strands
69 structural basis
70 structure
71 surface
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