DNA damage detection in nucleosomes involves DNA register shifting View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-05-29

AUTHORS

Syota Matsumoto, Simone Cavadini, Richard D. Bunker, Ralph S. Grand, Alessandro Potenza, Julius Rabl, Junpei Yamamoto, Andreas D. Schenk, Dirk Schübeler, Shigenori Iwai, Kaoru Sugasawa, Hitoshi Kurumizaka, Nicolas H. Thomä

ABSTRACT

Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are recognized in chromatin, in which nucleosomes restrict access to DNA. Here we report cryo-electron microscopy structures of UV-DDB bound to nucleosomes bearing a 6–4 pyrimidine–pyrimidone dimer or a DNA-damage mimic in various positions. We find that UV-DDB binds UV-damaged nucleosomes at lesions located in the solvent-facing minor groove without affecting the overall nucleosome architecture. In the case of buried lesions that face the histone core, UV-DDB changes the predominant translational register of the nucleosome and selectively binds the lesion in an accessible, exposed position. Our findings explain how UV-DDB detects occluded lesions in strongly positioned nucleosomes, and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise occluded sites in nucleosomal DNA. More... »

PAGES

79-84

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41586-019-1259-3

DOI

http://dx.doi.org/10.1038/s41586-019-1259-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1115972969

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/31142837


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39 DNA replication
40 DNA-binding proteins
41 Register
42 UV-DDB
43 access
44 architecture
45 cases
46 chromatin
47 core
48 cryo-electron microscopy structure
49 damage detection
50 detection
51 detects
52 dimers
53 exposure
54 findings
55 gene regulation
56 genome
57 groove
58 high-affinity DNA-binding proteins
59 histone core
60 humans
61 lesions
62 mechanism
63 microscopy structure
64 mimics
65 minor groove
66 nucleosomal DNA
67 nucleosome architecture
68 nucleosomes
69 position
70 positioned nucleosomes
71 protein
72 pyrimidine dimers
73 pyrimidine-pyrimidone dimers
74 regulation
75 repair
76 replication
77 sites
78 structure
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