Systems Based Mapping Demonstrates That Recovery from Alkylation Damage Requires DNA Repair, RNA Processing, and Translation Associated Networks

Overview

Journal Genomics

Specialty Genetics

Date 2008 Oct 1

PMID 18824089

Citations 14

Authors

John P Rooney

Ajish D George

Ashish Patil

Ulrike Begley

Erin Bessette

Maria R Zappala

Xin Huang

Douglas S Conklin

Richard P Cunningham

Thomas J Begley

Affiliations

Soon will be listed here.

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.

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References

Chen J, Samson L . Induction of S.cerevisiae MAG 3-methyladenine DNA glycosylase transcript levels in response to DNA damage. Nucleic Acids Res. 1991; 19(23):6427-32. PMC: 329188. DOI: 10.1093/nar/19.23.6427. View

Gunsalus K, Ge H, Schetter A, Goldberg D, Han J, Hao T . Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis. Nature. 2005; 436(7052):861-5. DOI: 10.1038/nature03876. View

Liebler D . Proteomic approaches to characterize protein modifications: new tools to study the effects of environmental exposures. Environ Health Perspect. 2002; 110 Suppl 1:3-9. PMC: 1241143. DOI: 10.1289/ehp.02110s113. View

Potter P, Wilkinson M, Fitton J, Carr F, Brennand J, Cooper D . Characterisation and nucleotide sequence of ogt, the O6-alkylguanine-DNA-alkyltransferase gene of E. coli. Nucleic Acids Res. 1987; 15(22):9177-93. PMC: 306461. DOI: 10.1093/nar/15.22.9177. View

Duncan T, Trewick S, Koivisto P, Bates P, Lindahl T, Sedgwick B . Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci U S A. 2002; 99(26):16660-5. PMC: 139200. DOI: 10.1073/pnas.262589799. View

Shin N, Liu Q, Stamer S, Liebler D . Protein targets of reactive electrophiles in human liver microsomes. Chem Res Toxicol. 2007; 20(6):859-67. PMC: 2556149. DOI: 10.1021/tx700031r. View

Kataoka H, Yamamoto Y, Sekiguchi M . A new gene (alkB) of Escherichia coli that controls sensitivity to methyl methane sulfonate. J Bacteriol. 1983; 153(3):1301-7. PMC: 221777. DOI: 10.1128/jb.153.3.1301-1307.1983. View

Aravind L, Koonin E . The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases. Genome Biol. 2001; 2(3):RESEARCH0007. PMC: 30706. DOI: 10.1186/gb-2001-2-3-research0007. View

Rudd K . EcoGene: a genome sequence database for Escherichia coli K-12. Nucleic Acids Res. 1999; 28(1):60-4. PMC: 102481. DOI: 10.1093/nar/28.1.60. View

10.

Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M . Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol. 2006; 2:2006.0008. PMC: 1681482. DOI: 10.1038/msb4100050. View

11.

Nakatsuru Y, Matsukuma S, Sekiguchi M, Ishikawa T . Characterization of O6-methylguanine-DNA methyltransferase in transgenic mice introduced with the E. coli ada gene. Mutat Res. 1991; 254(3):225-30. DOI: 10.1016/0921-8777(91)90060-3. View

12.

Smith G, Grisham J . Cytotoxicity of monofunctional alkylating agents. Methyl methanesulfonate and methyl-N'-nitro-N-nitrosoguanidine have different mechanisms of toxicity for 10T1/2 cells. Mutat Res. 1983; 111(3):405-17. DOI: 10.1016/0027-5107(83)90036-2. View

13.

Boiteux S, Huisman O, Laval J . 3-Methyladenine residues in DNA induce the SOS function sfiA in Escherichia coli. EMBO J. 1984; 3(11):2569-73. PMC: 557731. DOI: 10.1002/j.1460-2075.1984.tb02175.x. View

14.

Jelinsky S, Estep P, Church G, Samson L . Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with proteasomes. Mol Cell Biol. 2000; 20(21):8157-67. PMC: 86425. DOI: 10.1128/MCB.20.21.8157-8167.2000. View

15.

Leszczyniecka M, Kang D, Sarkar D, Su Z, Holmes M, Valerie K . Identification and cloning of human polynucleotide phosphorylase, hPNPase old-35, in the context of terminal differentiation and cellular senescence. Proc Natl Acad Sci U S A. 2002; 99(26):16636-41. PMC: 139196. DOI: 10.1073/pnas.252643699. View

16.

Sekiguchi M, Sanada M . Alkylation carcinogenesis in mice with altered levels of DNA repair methyltransferase. Prog Exp Tumor Res. 1999; 35:25-36. DOI: 10.1159/000062015. View

17.

Evensen G, Seeberg E . Adaptation to alkylation resistance involves the induction of a DNA glycosylase. Nature. 1982; 296(5859):773-5. DOI: 10.1038/296773a0. View

18.

Ideker T, Thorsson V, Ranish J, Christmas R, Buhler J, Eng J . Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science. 2001; 292(5518):929-34. DOI: 10.1126/science.292.5518.929. View

19.

Boffa L, Bolognesi C . Methylating agents: their target amino acids in nuclear proteins. Carcinogenesis. 1985; 6(9):1399-401. DOI: 10.1093/carcin/6.9.1399. View

20.

Begley T, Rosenbach A, Ideker T, Samson L . Hot spots for modulating toxicity identified by genomic phenotyping and localization mapping. Mol Cell. 2004; 16(1):117-25. DOI: 10.1016/j.molcel.2004.09.005. View