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Roles of DNA adenine methylation in host-pathogen interactions: mismatch repair, transcriptional regulation, and more

Martin G Marinus1, Josep Casadesus

  • 1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts, Worcester, USA.

FEMS Microbiology Reviews
|January 30, 2009
PubMed

Insights

DNA adenine methyltransferase (Dam) and cell cycle-regulated methyltransferase (CcrM) are epigenetic enzymes. They regulate gene expression and host-pathogen interactions, impacting DNA stability and protein binding.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Genomics

Background:

  • DNA adenine methyltransferase (Dam) in Gammaproteobacteria and cell cycle-regulated methyltransferase (CcrM) in Alphaproteobacteria perform similar DNA methylation.
  • Both enzymes methylate adenosine moieties using S-adenosyl-methionine, targeting GATC and GANTC sequences, respectively.
  • These methyltransferases likely evolved from ancestral restriction-modification systems, now solely dedicated to epigenetic genome modification.

Purpose of the Study:

  • To explore the evolutionary origins and functional roles of Dam and CcrM methylases.
  • To investigate how DNA methylation by Dam and CcrM influences DNA structure and protein interactions.
  • To understand the involvement of Dam and CcrM in host-pathogen interactions and virulence gene regulation.

Main Methods:

  • Comparative analysis of Dam and CcrM enzymes and their DNA targets.
  • Biophysical studies on the effects of 6-methyladenine on DNA stability and curvature.
  • Examination of DNA-protein interactions influenced by methylation states.
  • Investigation of Dam and CcrM roles in host-pathogen systems, including virulence gene regulation.

Main Results:

  • Dam and CcrM, despite independent origins, catalyze similar methylation reactions at related DNA sites.
  • DNA methylation by these enzymes alters DNA thermodynamic stability and curvature, affecting DNA-protein binding.
  • Methylation influences key processes like DNA replication initiation, mismatch repair, and transcription regulation.
  • Emerging evidence highlights the roles of Dam and CcrM in host-pathogen interactions, particularly Dam's regulation of virulence genes.

Conclusions:

  • Dam and CcrM are crucial epigenetic regulators with significant impacts on DNA structure and function.
  • These methyltransferases play diverse roles in bacterial biology, including gene regulation and host-pathogen dynamics.
  • Further research into Dam and CcrM functions, especially in virulence, is warranted for understanding bacterial pathogenesis.

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