Conditional epistatic interaction maps reveal global functional rewiring of genome integrity pathways in escherichia coli
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- dc.contributor.author Kumar, Ashwanica
- dc.contributor.author Beloglazova, Nataliaca
- dc.contributor.author Bundalovic-Torma, Cedoljubca
- dc.contributor.author Phanse, Sadhnaca
- dc.contributor.author Deineko, Viktorca
- dc.contributor.author Gagarinova, Allaca
- dc.contributor.author Musso, Gabrielca
- dc.contributor.author Vlasblom, Jamesca
- dc.contributor.author Lemak, Sofiaca
- dc.contributor.author Hooshyar, Mohsenca
- dc.contributor.author Minic, Zoranca
- dc.contributor.author Wagih, Omarca
- dc.contributor.author Mosca, Robertoca
- dc.contributor.author Aloy, Patrick, 1972-ca
- dc.contributor.author Golshani, Ashkanca
- dc.contributor.author Parkinson, Johnca
- dc.contributor.author Emili, Andrewca
- dc.contributor.author Yakunin, Alexander F.ca
- dc.contributor.author Babu, M. Madanca
- dc.date.accessioned 2016-06-02T17:27:31Z
- dc.date.available 2016-06-02T17:27:31Z
- dc.date.issued 2016
- dc.description.abstract As antibiotic resistance is increasingly becoming a public health concern, an improved understanding of the bacterial DNA damage response (DDR), which is commonly targeted by antibiotics, could be of tremendous therapeutic value. Although the genetic components of the bacterial DDR have been studied extensively in isolation, how the underlying biological pathways interact functionally remains unclear. Here, we address this by performing systematic, unbiased, quantitative synthetic genetic interaction (GI) screens and uncover widespread changes in the GI network of the entire genomic integrity apparatus of Escherichia coli under standard and DNA-damaging growth conditions. The GI patterns of untreated cultures implicated two previously uncharacterized proteins (YhbQ and YqgF) as nucleases, whereas reorganization of the GI network after DNA damage revealed DDR roles for both annotated and uncharacterized genes. Analyses of pan-bacterial conservation patterns suggest that DDR mechanisms and functional relationships are near universal, highlighting a modular and highly adaptive genomic stress response.ca
- dc.description.sponsorship This work was supported by grants from the Canadian Institutes of Health Research (CIHR) to A.E. (MOP-82852); Natural Sciences and Engineering Research Council (NSERC) Strategic Network grant IBN to A.F.Y.; NSERC Discovery to A. Golshani, J.P. (DG-06664), and M.B. (DG-20234); as well as the Canada Foundation for Innovation to M.B. J.V. is supported by the Saskatchewan Health Research Foundation Postdoctoral Research Fellowship, and M.B. holds a CIHR New Investigator award.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Kumar A, Beloglazova N, Bundalovic-Torma C, Phanse S, Deineko V, Gagarinova A et al. Conditional epistatic interaction maps reveal global functional rewiring of genome integrity pathways in escherichia coli. Cell Reports. 2016; 14(3): 648-661. DOI 10.1016/j.celrep.2015.12.060ca
- dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2015.12.060
- dc.identifier.issn 2211-1247
- dc.identifier.uri http://hdl.handle.net/10230/26810
- dc.language.iso engca
- dc.publisher Elsevierca
- dc.relation.ispartof Cell Reports. 2016; 14(3): 648-661
- dc.rights © 2016 The authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ca
- dc.subject.other Escheríchia colica
- dc.title Conditional epistatic interaction maps reveal global functional rewiring of genome integrity pathways in escherichia colica
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca