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Sci Rep. 2014 Oct 16;4:6642. doi: 10.1038/srep06642.

DNA phosphorothioate modifications influence the global transcriptional response and protect DNA from double-stranded breaks.

Author information

1
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
2
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.
3
Nextomics Biosciences Co., Ltd., Wuhan, China.

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.

PMID:
25319634
PMCID:
PMC4198939
DOI:
10.1038/srep06642
[Indexed for MEDLINE]
Free PMC Article

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