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

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

doi:10.1016/j.isci.2022.104040

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

iScience. 2022 Mar 9;25(4):104040. doi: 10.1016/j.isci.2022.104040. eCollection 2022 Apr 15.

Authors

Masayuki Kusakabe¹, Erina Kakumu^{1

2}, Fumika Kurihara^{1

2}, Kazuki Tsuchida^{1

2}, Takumi Maeda^{1

2}, Haruto Tada^{1

2}, Kanako Kusao^{1

2}, Akari Kato^{1

2}, Takeshi Yasuda³, Tomonari Matsuda⁴, Mitsuyoshi Nakao⁵, Masayuki Yokoi^{1

2}, Wataru Sakai^{1

2}, Kaoru Sugasawa^{1

2}

Affiliations

¹ Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
² Graduate School of Science, Kobe University, Kobe 657-8501, Japan.
³ Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan.
⁴ Research Center for Environmental Quality Management, Graduate School of Engineering, Kyoto University, Otsu 520-0811, Japan.
⁵ Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.

Abstract

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.

Keywords: Cell biology; Molecular biology; Molecular interaction.