Mechanism and regulation of DNA damage recognition in nucleotide excision repair

Autor: Shigenori Iwai, Haruto Tada, Kaoru Sugasawa, Yuki Onishi, Fumika Kurihara, Mari T. Furukawa, Wataru Sakai, Kanako Kusao, Masayuki Kusakabe, Masayuki Yokoi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Genes and Environment, Vol 41, Iss 1, Pp 1-6 (2019)
Genes and Environment
ISSN: 1880-7062
DOI: 10.1186/s41021-019-0119-6
Popis: Nucleotide excision repair (NER) is a versatile DNA repair pathway, which can remove an extremely broad range of base lesions from the genome. In mammalian global genomic NER, the XPC protein complex initiates the repair reaction by recognizing sites of DNA damage, and this depends on detection of disrupted/destabilized base pairs within the DNA duplex. A model has been proposed that XPC first interacts with unpaired bases and then the XPD ATPase/helicase in concert with XPA verifies the presence of a relevant lesion by scanning a DNA strand in 5′-3′ direction. Such multi-step strategy for damage recognition would contribute to achieve both versatility and accuracy of the NER system at substantially high levels. In addition, recognition of ultraviolet light (UV)-induced DNA photolesions is facilitated by the UV-damaged DNA-binding protein complex (UV-DDB), which not only promotes recruitment of XPC to the damage sites, but also may contribute to remodeling of chromatin structures such that the DNA lesions gain access to XPC and the following repair proteins. Even in the absence of UV-DDB, however, certain types of histone modifications and/or chromatin remodeling could occur, which eventually enable XPC to find sites with DNA lesions. Exploration of novel factors involved in regulation of the DNA damage recognition process is now ongoing.
Databáze: OpenAIRE
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