Histone deacetylation regulates nucleotide excision repair through an interaction with the XPC protein

Autor: Masayuki Kusakabe, Erina Kakumu, Fumika Kurihara, Kazuki Tsuchida, Takumi Maeda, Haruto Tada, Kanako Kusao, Akari Kato, Takeshi Yasuda, Tomonari Matsuda, Mitsuyoshi Nakao, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: iScience, Vol 25, Iss 4, Pp 104040- (2022)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2022.104040
Popis: Summary: The XPC protein complex plays a central role in DNA lesion recognition for global genome nucleotide excision repair (GG-NER). Lesion recognition can be accomplished in either a UV-DDB-dependent or -independent manner; however, it is unclear how these sub-pathways are regulated in chromatin. Here, we show that histone deacetylases 1 and 2 facilitate UV-DDB-independent recruitment of XPC to DNA damage by inducing histone deacetylation. XPC localizes to hypoacetylated chromatin domains in a DNA damage-independent manner, mediated by its structurally disordered middle (M) region. The M region interacts directly with the N-terminal tail of histone H3, an interaction compromised by H3 acetylation. Although the M region is dispensable for in vitro NER, it promotes DNA damage removal by GG-NER in vivo, particularly in the absence of UV-DDB. We propose that histone deacetylation around DNA damage facilitates the recruitment of XPC through the M region, contributing to efficient lesion recognition and initiation of GG-NER.
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