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PMID: 18824089 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Genomics ·Vol. 93 ·No. 1 ·2009-01-00 ·Pages 42-51

Rooney JP, George AD, Patil A, Begley U, Bessette E, Zappala MR, Huang X, Conklin DS, Cunningham RP, Begley TJ

Abstract

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.

MeSH Terms
Alkylation DNA Damage DNA Repair Escherichia coli/drug effects,genetics,metabolism Escherichia coli Proteins/genetics,metabolism Gene Deletion Genome, Bacterial Methyl Methanesulfonate/pharmacology Mutagens/pharmacology Mutation Phenotype Protein Biosynthesis Systems Biology Transcription, Genetic
Chemicals
Escherichia coli Proteins Mutagens Methyl Methanesulfonate
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Rooney John P
Department of Biomedical Sciences, University at Albany, State University of New York, Rensselaer, NY 12144-3456, USA.
George Ajish D
Patil Ashish
Begley Ulrike
Bessette Erin
Zappala Maria R
Huang Xin
Conklin Douglas S
Cunningham Richard P
Begley Thomas J
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Article Info
Journal
Genomics
Abbr.
Genomics
ISSN
1089-8646
DOI
10.1016/j.ygeno.2008.09.001
Published
2009-01-00
Epub
2008-00-16
Pages
42-51
Language
English
Region
United States
NLM ID
8800135
PMCID
PMC2633870
Subset
IM
Grants
NIEHS NIH HHS · R01 ES015037 · United States
NIEHS NIH HHS · 1K22ES01225101 · United States
PHS HHS · CRR1C06RR0154464 · United States
NIEHS NIH HHS · 1R01ES015037 · United States
NIEHS NIH HHS · R01 ES015037-01 · United States
NIEHS NIH HHS · K22 ES012251 · United States
NIEHS NIH HHS · K22 ES012251-02 · United States
NIGMS NIH HHS · R01 GM046312 · United States
NIGMS NIH HHS · GM46312 · United States
External Links
PubMed source DOI: 10.1016/j.ygeno.2008.09.001 PMC Full Text View journal details
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