4YM5

Crystal structure of the human nucleosome containing 6-4PP (inside)

Summary for 4YM5

• Entry DOI: 10.2210/pdb4ym5/pdb
• Related: 4YM6
• Descriptor: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (6 entities in total)
• Functional Keywords: (6-4) photoproduct, nucleosome, histone, dna binding, structural protein-dna complex, structural protein/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 201614.29

Authors

Osakabe, A.,Tachiwana, H.,Kagawa, W.,Horikoshi, N.,Matsumoto, S.,Hasegawa, M.,Matsumoto, N.,Toga, T.,Yamamoto, J.,Hanaoka, F.,Thoma, N.H.,Sugasawa, K.,Iwai, S.,Kurumizaka, H. (deposition date: 2015-03-06, release date: 2015-12-02, Last modification date: 2023-11-08)

Primary citation

Osakabe, A.,Tachiwana, H.,Kagawa, W.,Horikoshi, N.,Matsumoto, S.,Hasegawa, M.,Matsumoto, N.,Toga, T.,Yamamoto, J.,Hanaoka, F.,Thoma, N.H.,Sugasawa, K.,Iwai, S.,Kurumizaka, H.
Structural basis of pyrimidine-pyrimidone (6-4) photoproduct recognition by UV-DDB in the nucleosome
Sci Rep, 5:16330-16330, 2015

PubMed 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.

PubMed: 26573481
DOI: 10.1038/srep16330

Experimental method

X-RAY DIFFRACTION (4.005 Å)