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

作者：Osakabe Akihisa; Tachiwana Hiroaki; Kagawa Wataru; Horikoshi Naoki; Matsumoto Syota; Hasegawa Mayu; Matsumoto Naoyuki; Toga Tatsuya; Yamamoto Junpei; Hanaoka Fumio; Thomae Nicolas H; Sugasawa Kaoru; Iwai Shigenori; Kurumizaka Hitoshi^*

来源：Scientific Reports, 2015, 5(1): 16330.

DOI：10.1038/srep16330

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.

• 出版日期2015-11-17