Systems based mapping demonstrates that recovery from alkylation damage requires DNA repair, RNA processing, and translation associated networks

Genomics. 2009 Jan;93(1):42-51. doi: 10.1016/j.ygeno.2008.09.001. Epub 2008 Oct 16.


The identification of cellular responses to damage can promote mechanistic insight into stress signalling. We have screened a library of 3968 Escherichia coli gene-deletion mutants to identify 99 gene products that modulate the toxicity of the alkylating agent methyl methanesulfonate (MMS). We have developed an ontology mapping approach to identify functional categories over-represented with MMS-toxicity modulating proteins and demonstrate that, in addition to DNA re-synthesis (replication, recombination, and repair), proteins involved in mRNA processing and translation influence viability after MMS damage. We have also mapped our MMS-toxicity modulating proteins onto an E. coli protein interactome and identified a sub-network consisting of 32 proteins functioning in DNA repair, mRNA processing, and translation. Clustering coefficient analysis identified seven highly connected MMS-toxicity modulating proteins associated with translation and mRNA processing, with the high connectivity suggestive of a coordinated response. Corresponding results from reporter assays support the idea that the SOS response is influenced by activities associated with the mRNA-translation interface.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • DNA Damage*
  • DNA Repair*
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Gene Deletion
  • Genome, Bacterial
  • Methyl Methanesulfonate / pharmacology*
  • Mutagens / pharmacology
  • Mutation
  • Phenotype
  • Protein Biosynthesis
  • Systems Biology*
  • Transcription, Genetic


  • Escherichia coli Proteins
  • Mutagens
  • Methyl Methanesulfonate