Xeroderma pigmentosum group C protein interacts with histones: regulation by acetylated states of histone H3

Erina Kakumu, Seiya Nakanishi, Hiromi M. Shiratori, Akari Kato, Wataru Kobayashi, Shinichi Machida, Takeshi Yasuda, Naoko Adachi, Naoaki Saito, Tsuyoshi Ikura, Hitoshi Kurumizaka, Hiroshi Kimura, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    22 Citations (Scopus)

    Abstract

    In the mammalian global genome nucleotide excision repair pathway, two damage recognition factors, XPC and UV-DDB, play pivotal roles in the initiation of the repair reaction. However, the molecular mechanisms underlying regulation of the lesion recognition process in the context of chromatin structures remain to be understood. Here, we show evidence that damage recognition factors tend to associate with chromatin regions devoid of certain types of acetylated histones. Treatment of cells with histone deacetylase inhibitors retarded recruitment of XPC to sites of UV-induced DNA damage and the subsequent repair process. Biochemical studies showed novel multifaceted interactions of XPC with histone H3, which were profoundly impaired by deletion of the N-terminal tail of histone H3. In addition, histone H1 also interacted with XPC. Importantly, acetylation of histone H3 markedly attenuated the interaction with XPC in vitro, and local UV irradiation of cells decreased the level of H3K27ac in the damaged areas. Our results suggest that histone deacetylation plays a significant role in the process of DNA damage recognition for nucleotide excision repair and that the localization and functions of XPC can be regulated by acetylated states of histones.

    Original languageEnglish
    Pages (from-to)310-327
    Number of pages18
    JournalGenes to Cells
    Volume22
    Issue number3
    DOIs
    Publication statusPublished - 2017 Mar 1

    ASJC Scopus subject areas

    • Genetics
    • Cell Biology

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