Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli
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...
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2016-01-01
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doaj-9fbd82c0796d4664a9c936ea2215594d2020-11-24T22:01:24ZengElsevierCell Reports2211-12472016-01-0114364866110.1016/j.celrep.2015.12.060Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coliAshwani Kumar0Natalia Beloglazova1Cedoljub Bundalovic-Torma2Sadhna Phanse3Viktor Deineko4Alla Gagarinova5Gabriel Musso6James Vlasblom7Sofia Lemak8Mohsen Hooshyar9Zoran Minic10Omar Wagih11Roberto Mosca12Patrick Aloy13Ashkan Golshani14John Parkinson15Andrew Emili16Alexander F. Yakunin17Mohan Babu18Department of Computer Science, University of Regina, Regina, SK S4S 0A2, CanadaDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, CanadaHospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, CanadaTerrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, CanadaDepartment of Biochemistry, University of Regina, Regina, SK S4S 0A2, CanadaTerrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, CanadaDepartment of Medicine, Harvard Medical School and Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA 02115, USADepartment of Biochemistry, University of Regina, Regina, SK S4S 0A2, CanadaDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, CanadaDepartment of Biology, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Biochemistry, University of Regina, Regina, SK S4S 0A2, CanadaTerrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, CanadaJoint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, c/Baldiri i Reixac 10-12, Barcelona, 08028, Catalonia, SpainJoint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, c/Baldiri i Reixac 10-12, Barcelona, 08028, Catalonia, SpainDepartment of Biology, Carleton University, Ottawa, ON K1S 5B6, CanadaHospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, CanadaTerrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, CanadaDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, CanadaDepartment of Biochemistry, University of Regina, Regina, SK S4S 0A2, CanadaAs 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.http://www.sciencedirect.com/science/article/pii/S2211124715015016 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ashwani Kumar Natalia Beloglazova Cedoljub Bundalovic-Torma Sadhna Phanse Viktor Deineko Alla Gagarinova Gabriel Musso James Vlasblom Sofia Lemak Mohsen Hooshyar Zoran Minic Omar Wagih Roberto Mosca Patrick Aloy Ashkan Golshani John Parkinson Andrew Emili Alexander F. Yakunin Mohan Babu |
spellingShingle |
Ashwani Kumar Natalia Beloglazova Cedoljub Bundalovic-Torma Sadhna Phanse Viktor Deineko Alla Gagarinova Gabriel Musso James Vlasblom Sofia Lemak Mohsen Hooshyar Zoran Minic Omar Wagih Roberto Mosca Patrick Aloy Ashkan Golshani John Parkinson Andrew Emili Alexander F. Yakunin Mohan Babu Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli Cell Reports |
author_facet |
Ashwani Kumar Natalia Beloglazova Cedoljub Bundalovic-Torma Sadhna Phanse Viktor Deineko Alla Gagarinova Gabriel Musso James Vlasblom Sofia Lemak Mohsen Hooshyar Zoran Minic Omar Wagih Roberto Mosca Patrick Aloy Ashkan Golshani John Parkinson Andrew Emili Alexander F. Yakunin Mohan Babu |
author_sort |
Ashwani Kumar |
title |
Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli |
title_short |
Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli |
title_full |
Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli |
title_fullStr |
Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli |
title_full_unstemmed |
Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli |
title_sort |
conditional epistatic interaction maps reveal global functional rewiring of genome integrity pathways in escherichia coli |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-01-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124715015016 |
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