Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli
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
Affiliations
Ashwani Kumar
Department of Computer Science, University of Regina, Regina, SK S4S 0A2, Canada
Natalia Beloglazova
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada
Cedoljub Bundalovic-Torma
Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada
Sadhna Phanse
Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
Viktor Deineko
Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada
Alla Gagarinova
Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
Gabriel Musso
Department of Medicine, Harvard Medical School and Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA 02115, USA
James Vlasblom
Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada
Sofia Lemak
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada
Mohsen Hooshyar
Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
Zoran Minic
Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada
Omar Wagih
Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
Roberto Mosca
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
Patrick Aloy
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
Ashkan Golshani
Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
John Parkinson
Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada
Andrew Emili
Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
Alexander F. Yakunin
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada
Mohan Babu
Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada
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.