ニシ　リョウタロウ   西　良太郎    所属   応用生物学部 応用生物学科    職種   准教授
言語種別	英語
発行・発表の年月	2017/03
形態種別	学術論文
査読	査読あり
標題	Thymine DNA glycosylase modulates the DNA damage response and gene expression by base excision repair-dependent and -independent mechanisms.
執筆形態	共著
掲載誌名	Genes to Cells
掲載区分	国外
出版社・発行元	Wiley
巻・号・頁	22,pp.392-405
総ページ数	14
著者・共著者	Tomohumi Nakamura, Kouichi Murakami, Haruto Tada, Yoshihiko Uehara, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Hisato Saitoh, Hideo Nishitani, Tetsuya Ono, Ryotaro Nishi, Masayuki Yokoi, Wataru Sakai, and Kaoru Sugasawa
概要	Thymine DNA glycosylase (TDG) is a base excision repair (BER) enzyme, which is implicated in correction of deamination-induced DNA mismatches, the DNA demethylation process, and regulation of gene expression. Because of these pivotal roles associated, it is crucial to elucidate how the TDG functions are appropriately regulated in vivo. Here we present evidence that the TDG protein undergoes degradation upon various types of DNA damage, including ultraviolet light (UV). The UV-induced degradation of TDG was dependent on proficiency in nucleotide excision repair and on CRL4CDT2-mediated ubiquitination that requires a physical interaction between TDG and DNA polymerase clamp PCNA. Using the Tdg-deficient mouse embryonic fibroblasts, we found that ectopic expression of TDG compromised cellular survival after UV irradiation and repair of UV-induced DNA lesions. These negative effects on cellular UV responses were alleviated by introducing mutations in TDG that impaired its BER function. The expression of TDG induced a large-scale alteration in the gene expression profile independently of its DNA glysocylase activity, whereas a subset of genes were affected by the catalytic activity of TDG. Our results indicate the presence of BER-dependent and independent functions of TDG, which are involved in regulation of cellular DNA damage responses and gene expression patterns.
DOI	https://doi.org/10.1111/gtc.12481
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