title: Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli.
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.
authors.affiliation: Department of Computer Science, University of Regina, Regina, SK S4S 0A2, Canada.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.
authors.forename: Natalia
authors.initials: N
authors.lastname: Beloglazova
authors.affiliation: Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Cedoljub
authors.initials: C
authors.lastname: Bundalovic-Torma
authors.affiliation: Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Phanse
authors.affiliation: Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.
authors.forename: Viktor
authors.initials: V
authors.lastname: Deineko
authors.affiliation: Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
authors.forename: Alla
authors.initials: A
authors.lastname: Gagarinova
authors.affiliation: Department of Medicine, Harvard Medical School and Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Musso
authors.affiliation: Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Vlasblom
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.
authors.forename: Sofia
authors.initials: S
authors.lastname: Lemak
authors.affiliation: Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Hooshyar
authors.affiliation: Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Minic
authors.affiliation: Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
authors.forename: Omar
authors.initials: O
authors.lastname: Wagih
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mosca
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aloy
authors.affiliation: Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Golshani
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Parkinson
authors.affiliation: Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Emili
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Yakunin
authors.affiliation: Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada. Electronic address: mohan.babu@uregina.ca.
authors.forename: Mohan
authors.initials: M
authors.lastname: Babu
mesh_terms: D020134:Catalytic Domain; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D003851:Deoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053263:Gene Regulatory Networks; D016296:Mutagenesis; D012313:RNA / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D012313:RNA; D004247:DNA; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; C470945:YqgF protein, E coli