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Cell Rep. 2016 Jan 26;14(3):648-661. doi: 10.1016/j.celrep.2015.12.060. Epub 2016 Jan 8.

Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli.

Author information

1
Department of Computer Science, University of Regina, Regina, SK S4S 0A2, Canada.
2
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.
3
Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
4
Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.
5
Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.
6
Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
7
Department of Medicine, Harvard Medical School and Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
8
Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.
9
Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
10
Joint 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, Spain.
11
Joint 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, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, Barcelona, 08010, Catalonia, Spain.
12
Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
13
Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
14
Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada. Electronic address: mohan.babu@uregina.ca.

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.

PMID:
26774489
DOI:
10.1016/j.celrep.2015.12.060
[Indexed for MEDLINE]
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