Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.

DNA methylation plays central roles in diverse cellular processes, ranging from error-correction during replication to regulation of bacterial defense mechanisms. Nevertheless, certain aberrant methylation modifications can have lethal consequences. The mechanisms by which bacteria detect and respon...

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Main Authors: Aditya Kamat, Ngat T Tran, Mohak Sharda, Neha Sontakke, Tung B K Le, Anjana Badrinarayanan
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-03-01
Series:PLoS Biology
Online Access:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002540&type=printable
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author Aditya Kamat
Ngat T Tran
Mohak Sharda
Neha Sontakke
Tung B K Le
Anjana Badrinarayanan
author_facet Aditya Kamat
Ngat T Tran
Mohak Sharda
Neha Sontakke
Tung B K Le
Anjana Badrinarayanan
author_sort Aditya Kamat
collection DOAJ
description DNA methylation plays central roles in diverse cellular processes, ranging from error-correction during replication to regulation of bacterial defense mechanisms. Nevertheless, certain aberrant methylation modifications can have lethal consequences. The mechanisms by which bacteria detect and respond to such damage remain incompletely understood. Here, we discover a highly conserved but previously uncharacterized transcription factor (Cada2), which orchestrates a methylation-dependent adaptive response in Caulobacter. This response operates independently of the SOS response, governs the expression of genes crucial for direct repair, and is essential for surviving methylation-induced damage. Our molecular investigation of Cada2 reveals a cysteine methylation-dependent posttranslational modification (PTM) and mode of action distinct from its Escherichia coli counterpart, a trait conserved across all bacteria harboring a Cada2-like homolog instead. Extending across the bacterial kingdom, our findings support the notion of divergence and coevolution of adaptive response transcription factors and their corresponding sequence-specific DNA motifs. Despite this diversity, the ubiquitous prevalence of adaptive response regulators underscores the significance of a transcriptional switch, mediated by methylation PTM, in driving a specific and essential bacterial DNA damage response.
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issn 1544-9173
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publishDate 2024-03-01
publisher Public Library of Science (PLoS)
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spelling doaj-art-647ee7a5b65142d483987dafdbb712232025-08-20T02:22:59ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-03-01223e300254010.1371/journal.pbio.3002540Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.Aditya KamatNgat T TranMohak ShardaNeha SontakkeTung B K LeAnjana BadrinarayananDNA methylation plays central roles in diverse cellular processes, ranging from error-correction during replication to regulation of bacterial defense mechanisms. Nevertheless, certain aberrant methylation modifications can have lethal consequences. The mechanisms by which bacteria detect and respond to such damage remain incompletely understood. Here, we discover a highly conserved but previously uncharacterized transcription factor (Cada2), which orchestrates a methylation-dependent adaptive response in Caulobacter. This response operates independently of the SOS response, governs the expression of genes crucial for direct repair, and is essential for surviving methylation-induced damage. Our molecular investigation of Cada2 reveals a cysteine methylation-dependent posttranslational modification (PTM) and mode of action distinct from its Escherichia coli counterpart, a trait conserved across all bacteria harboring a Cada2-like homolog instead. Extending across the bacterial kingdom, our findings support the notion of divergence and coevolution of adaptive response transcription factors and their corresponding sequence-specific DNA motifs. Despite this diversity, the ubiquitous prevalence of adaptive response regulators underscores the significance of a transcriptional switch, mediated by methylation PTM, in driving a specific and essential bacterial DNA damage response.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002540&type=printable
spellingShingle Aditya Kamat
Ngat T Tran
Mohak Sharda
Neha Sontakke
Tung B K Le
Anjana Badrinarayanan
Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.
PLoS Biology
title Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.
title_full Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.
title_fullStr Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.
title_full_unstemmed Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.
title_short Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.
title_sort widespread prevalence of a methylation dependent switch to activate an essential dna damage response in bacteria
url https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002540&type=printable
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