A genomic Multiprocess survey of machineries that control and link cell shape, microtubule organization, and cell-cycle progression.
Understanding cells as integrated systems requires that we systematically decipher how single genes affect multiple biological processes and how processes are functionally linked. Here, we used multiprocess phenotypic profiling, combining high-resolution 3D confocal microscopy and multiparametric image analysis, to simultaneously survey the fission yeast genome with respect to three key cellular processes: cell shape, microtubule organization, and cell-cycle progression. We identify, validate, and functionally annotate 262 genes controlling specific aspects of those processes. Of these, 62% had not been linked to these processes before and 35% are implicated in multiple processes. Importantly, we identify a conserved role for DNA-damage responses in controlling microtubule stability. In addition, we investigate how the processes are functionally linked. We show unexpectedly that disruption of cell-cycle progression does not necessarily affect cell size control and that distinct aspects of cell shape regulate microtubules and vice versa, identifying important systems-level links across these processes.
The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, United Kingdom.|Genetics Department, University of Cambridge, Downing Street, Cambridge, CB2 3EH, United Kingdom.|Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, HPM G16.2, Zurich, CH-8093, Switzerland.
Veronika
V
Graml
The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, United Kingdom.|Genetics Department, University of Cambridge, Downing Street, Cambridge, CB2 3EH, United Kingdom.|Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, HPM G16.2, Zurich, CH-8093, Switzerland.
Xenia
X
Studera
The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, United Kingdom.|Genetics Department, University of Cambridge, Downing Street, Cambridge, CB2 3EH, United Kingdom.
Jonathan L D
JLD
Lawson
The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, United Kingdom.|Genetics Department, University of Cambridge, Downing Street, Cambridge, CB2 3EH, United Kingdom.
Anatole
A
Chessel
The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, United Kingdom.|Genetics Department, University of Cambridge, Downing Street, Cambridge, CB2 3EH, United Kingdom.
Marco
M
Geymonat
Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, HPM G16.2, Zurich, CH-8093, Switzerland.
Miriam
M
Bortfeld-Miller
Institut Curie, Centre for Computational Biology, Centre de Recherche Unité 900, 26 Rue d'Ulm, 75248 Paris, France.
Thomas
T
Walter
The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, United Kingdom.|Zoology Department, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, United Kingdom.
Laura
L
Wagstaff
The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, United Kingdom.|Zoology Department, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, United Kingdom.
Eugenia
E
Piddini
The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, United Kingdom.|Genetics Department, University of Cambridge, Downing Street, Cambridge, CB2 3EH, United Kingdom.|Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, HPM G16.2, Zurich, CH-8093, Switzerland.
Rafael E
RE
Carazo Salas
D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division; D048430:Cell Shape / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D005656:Fungal Proteins / Q000235:genetics; D055786:Gene Knockout Techniques; D021621:Imaging, Three-Dimensional; D018613:Microscopy, Confocal; D008870:Microtubules / Q000235:genetics* / Q000502:physiology; D021381:Protein Transport / Q000235:genetics; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins