title: ATP-dependent chromatin remodeling facilitates nucleotide excision repair of UV-induced DNA lesions in synthetic dinucleosomes.
abstract: To investigate the relationship between chromatin dynamics and nucleotide excision repair (NER), we have examined the effect of chromatin structure on the formation of two major classes of UV-induced DNA lesions in reconstituted dinucleosomes. Furthermore, we have developed a model chromatin-NER system consisting of purified human NER factors and dinucleosome substrates that contain pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) either at the center of the nucleosome or in the linker DNA. We have found that the two classes of UV-induced DNA lesions are formed efficiently at every location on dinucleosomes in a manner similar to that of naked DNA, even in the presence of histone H1. On the other hand, excision of 6-4PPs is strongly inhibited by dinucleosome assembly, even within the linker DNA region. These results provide direct evidence that the human NER machinery requires a space greater than the size of the linker DNA to excise UV lesions efficiently. Interestingly, NER dual incision in dinucleosomes is facilitated by recombinant ACF, an ATP-dependent chromatin remodeling factor. Our results indicate that there is a functional connection between chromatin remodeling and the initiation step of NER.
authors: Division of Gene Therapy Science, Osaka University School of Medicine, 2-2 Yamada-oka, Suita, Japan. kiyoeura@gts.med.osaka-u.ac.jp
authors: K
authors: K
authors: Ura
authors: M
authors: M
authors: Araki
authors: H
authors: H
authors: Saeki
authors: C
authors: C
authors: Masutani
authors: T
authors: T
authors: Ito
authors: S
authors: S
authors: Iwai
authors: T
authors: T
authors: Mizukoshi
authors: Y
authors: Y
authors: Kaneda
authors: F
authors: F
authors: Hanaoka
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D009707:Nucleosomes / Q000528:radiation effects*; D011740:Pyrimidine Dimers / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D002843:Chromatin; C086468:ISWI protein; D009707:Nucleosomes; D011740:Pyrimidine Dimers; D014157:Transcription Factors; C058406:pyrimidine-pyrimidone dimer; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases