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

Gan R, Wu X, He W, Liu Z, Wu S, Chen C, Chen S, Xiang Q, Deng Z, Liang D, Chen S, Wang L - Sci Rep (2014)

Bottom Line: In this study, we employed the RNA-seq analysis to characterize the global transcriptional changes in response to PT modifications.The DNA double-stranded breaks then trigger the SOS response, cell filamentation and prophage induction.Our data provide insights into the physiological role of the DNA PT system.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, 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.

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COG functional categories of the differentially expressed genes in dnd mutants.Each bar represents the actual number of genes (log2 ratio ≥ 1 and ≤−1, and with p-value<0.05). The COG categories are identified by capital letters as follows: C, energy production and conversion; D, cell cycle control, cell division and chromosome partitioning; E, amino acid transport and metabolism; F, nucleotide transport and metabolism; G, carbohydrate transport and metabolism; H, coenzyme transport and metabolism; I, lipid transport and metabolism; J, translation; K, transcription; L, replication; M, cell wall/membrane/envelope biogenesis; N, cell motility; O, posttranslational modification, protein turnover, chaperones; P, inorganic ion transport and metabolism; Q, secondary metabolites biosynthesis, transport and catabolism; R, general function prediction only; S, function unknown; T, signal transduction mechanisms; U, intracellular trafficking and secretion; V, defense mechanisms; and -, not in COGs. Note that since COG annotation groups overlap, the sum of COG annotated genes is larger than the number of total up- and down-regulated genes analyzed.
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f4: COG functional categories of the differentially expressed genes in dnd mutants.Each bar represents the actual number of genes (log2 ratio ≥ 1 and ≤−1, and with p-value<0.05). The COG categories are identified by capital letters as follows: C, energy production and conversion; D, cell cycle control, cell division and chromosome partitioning; E, amino acid transport and metabolism; F, nucleotide transport and metabolism; G, carbohydrate transport and metabolism; H, coenzyme transport and metabolism; I, lipid transport and metabolism; J, translation; K, transcription; L, replication; M, cell wall/membrane/envelope biogenesis; N, cell motility; O, posttranslational modification, protein turnover, chaperones; P, inorganic ion transport and metabolism; Q, secondary metabolites biosynthesis, transport and catabolism; R, general function prediction only; S, function unknown; T, signal transduction mechanisms; U, intracellular trafficking and secretion; V, defense mechanisms; and -, not in COGs. Note that since COG annotation groups overlap, the sum of COG annotated genes is larger than the number of total up- and down-regulated genes analyzed.

Mentions: The transcriptome analysis revealed that the SOS genes were not induced in XTG103 and XTG104; this result was consistent with the normal cellular morphology observed for those strains. XTG103 and XTG104 displayed similar transcriptional profiles, indicating a major contribution of dndFGHI to the global transcriptional changes (Fig. 1). XTG103 and XTG104 had 229 and 216 differentially transcribed genes, respectively, compared to the wild-type S. enterica, of which 186 genes shared common transcriptional patterns. The most significantly changed genes in XTG103 and XTG104 are in the energy production and conversion, carbohydrate transport and metabolism, transcription, function unknown, and unclassified COG groups (Fig. 4, Supplementary Data).


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

Gan R, Wu X, He W, Liu Z, Wu S, Chen C, Chen S, Xiang Q, Deng Z, Liang D, Chen S, Wang L - Sci Rep (2014)

COG functional categories of the differentially expressed genes in dnd mutants.Each bar represents the actual number of genes (log2 ratio ≥ 1 and ≤−1, and with p-value<0.05). The COG categories are identified by capital letters as follows: C, energy production and conversion; D, cell cycle control, cell division and chromosome partitioning; E, amino acid transport and metabolism; F, nucleotide transport and metabolism; G, carbohydrate transport and metabolism; H, coenzyme transport and metabolism; I, lipid transport and metabolism; J, translation; K, transcription; L, replication; M, cell wall/membrane/envelope biogenesis; N, cell motility; O, posttranslational modification, protein turnover, chaperones; P, inorganic ion transport and metabolism; Q, secondary metabolites biosynthesis, transport and catabolism; R, general function prediction only; S, function unknown; T, signal transduction mechanisms; U, intracellular trafficking and secretion; V, defense mechanisms; and -, not in COGs. Note that since COG annotation groups overlap, the sum of COG annotated genes is larger than the number of total up- and down-regulated genes analyzed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4198939&req=5

f4: COG functional categories of the differentially expressed genes in dnd mutants.Each bar represents the actual number of genes (log2 ratio ≥ 1 and ≤−1, and with p-value<0.05). The COG categories are identified by capital letters as follows: C, energy production and conversion; D, cell cycle control, cell division and chromosome partitioning; E, amino acid transport and metabolism; F, nucleotide transport and metabolism; G, carbohydrate transport and metabolism; H, coenzyme transport and metabolism; I, lipid transport and metabolism; J, translation; K, transcription; L, replication; M, cell wall/membrane/envelope biogenesis; N, cell motility; O, posttranslational modification, protein turnover, chaperones; P, inorganic ion transport and metabolism; Q, secondary metabolites biosynthesis, transport and catabolism; R, general function prediction only; S, function unknown; T, signal transduction mechanisms; U, intracellular trafficking and secretion; V, defense mechanisms; and -, not in COGs. Note that since COG annotation groups overlap, the sum of COG annotated genes is larger than the number of total up- and down-regulated genes analyzed.
Mentions: The transcriptome analysis revealed that the SOS genes were not induced in XTG103 and XTG104; this result was consistent with the normal cellular morphology observed for those strains. XTG103 and XTG104 displayed similar transcriptional profiles, indicating a major contribution of dndFGHI to the global transcriptional changes (Fig. 1). XTG103 and XTG104 had 229 and 216 differentially transcribed genes, respectively, compared to the wild-type S. enterica, of which 186 genes shared common transcriptional patterns. The most significantly changed genes in XTG103 and XTG104 are in the energy production and conversion, carbohydrate transport and metabolism, transcription, function unknown, and unclassified COG groups (Fig. 4, Supplementary Data).

Bottom Line: In this study, we employed the RNA-seq analysis to characterize the global transcriptional changes in response to PT modifications.The DNA double-stranded breaks then trigger the SOS response, cell filamentation and prophage induction.Our data provide insights into the physiological role of the DNA PT system.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, 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.

Show MeSH
Related in: MedlinePlus