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- Title
ATP-dependent chromatin remodeling facilitates nucleotide excision repair of UV-induced DNA lesions in synthetic dinucleosomes.
- Authors
Ura, Kiyoe; Araki, Marito; Saeki, Hideaki; Masutani, Chikahide; Ito, Takashi; Iwai, Shigenori; Mizukoshi, Toshimi; Kaneda, Vasufumi; Hanaoka, Fumio
- 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 dinucteosomes. 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 nucteosome or in the tinker DNA. We have found that the two classes of UV-induced DNA lesions are formed efficiently at every location on dinucteosomes 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 dinucteosome assembly, even within the tinker DNA region. These results provide direct evidence that the human NER machinery requires a space greater than the size of the tinker DNA to excise UV lesions efficiently. Interestingly, NER dual incision in dinucleosomes is facilitated by recombinant ACE, an ATP-dependent chromatin remodeling factor. Our results indicate that there is a functional connection between chromatin remodeling and the initiation step of NER.
- Subjects
CHROMATIN; CHROMOSOMES; NUCLEOPROTEINS; NUCLEOTIDES; NUCLEIC acids; PYRIMIDINES; HETEROCYCLIC compounds
- Publication
EMBO Journal, 2001, Vol 20, Issue 8, p2004
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/20.8.2004