title: Protease activity of PprI facilitates DNA damage response: Mn2+-dependence and substrate sequence-specificity of the proteolytic reaction.
abstract: The extremophilic bacterium Deinococcus radiodurans exhibits an extraordinary resistance to ionizing radiation. Previous studies established that a protein named PprI, which exists only in the Deinococcus-Thermus family, acts as a general switch to orchestrate the expression of a number of DNA damage response (DDR) proteins involved in cellular radio-resistance. Here we show that the regulatory mechanism of PprI depends on its Mn(2+)-dependent protease activity toward DdrO, a transcription factor that suppresses DDR genes' expression. Recognition sequence-specificity around the PprI cleavage site is essential for DNA damage repair in vivo. PprI and DdrO mediate a novel DNA damage response pathway differing from the classic LexA-mediated SOS response system found in radiation-sensitive bacterium Escherichia coli. This PprI-mediated pathway in D. radiodurans is indispensable for its extreme radio-resistance and therefore its elucidation significantly advances our understanding of the DNA damage repair mechanism in this amazing organism.
authors: Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, China.
authors: Yunguang
authors: Y
authors: Wang
authors: Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, China.
authors: Qiang
authors: Q
authors: Xu
authors: National Institute on Aging, Biomedical Research Center, National Institutes of Health, Baltimore, United States of America.
authors: Huiming
authors: H
authors: Lu
authors: Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, China.
authors: Lin
authors: L
authors: Lin
authors: Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, China.
authors: Liangyan
authors: L
authors: Wang
authors: Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, China.
authors: Hong
authors: H
authors: Xu
authors: Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, China.
authors: Xianyan
authors: X
authors: Cui
authors: Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, China.
authors: Hui
authors: H
authors: Zhang
authors: Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, China.
authors: Tingting
authors: T
authors: Li
authors: Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, China.
authors: Yuejin
authors: Y
authors: Hua
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D004249:DNA Damage; D034301:Deinococcus / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects; D005720:Gamma Rays; D008345:Manganese / Q000378:metabolism; D009154:Mutation; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D059748:Proteolysis; D013014:SOS Response, Genetics; D013379:Substrate Specificity; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D008345:Manganese; D010447:Peptide Hydrolases