title: DNA phosphorothioate modifications influence the global transcriptional response and protect DNA from double-stranded breaks.
abstract: The modification of DNA by phosphorothioate (PT) occurs when the non-bridging oxygen in the sugar-phosphate backbone of DNA is replaced with sulfur. This DNA backbone modification was recently discovered and is governed by the dndABCDE genes in a diverse group of bacteria and archaea. However, the biological function of DNA PT modifications is poorly understood. In this study, we employed the RNA-seq analysis to characterize the global transcriptional changes in response to PT modifications. Our results show that DNA without PT protection is susceptible to DNA damage caused by the dndFGHI gene products. The DNA double-stranded breaks then trigger the SOS response, cell filamentation and prophage induction. Heterologous expression of dndBCDE conferring DNA PT modifications at GPSA and GPST prevented the damage in Salmonella enterica. Our data provide insights into the physiological role of the DNA PT system.
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gan
authors.affiliation: 1] Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China [2] Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Nextomics Biosciences Co., Ltd., Wuhan, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
authors.forename: Shuangju
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
authors.forename: Qianrong
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Nextomics Biosciences Co., Ltd., Wuhan, China.
authors.forename: Dequan
authors.initials: D
authors.lastname: Liang
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
authors.forename: Lianrong
authors.initials: L
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000187:drug effects; D010100:Oxygen / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D054735:Phosphorothioate Oligonucleotides / Q000737:chemistry / Q000235:genetics*; D019779:Salmonella enterica / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D010710:Phosphates; D054735:Phosphorothioate Oligonucleotides; D004247:DNA; D010100:Oxygen; C035638:thiophosphoric acid