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G3 (Bethesda). 2017 Jun 7;7(6):1753-1766. doi: 10.1534/g3.117.042317.

Mapping the Synthetic Dosage Lethality Network of CDK1/CDC28.

Author information

1
Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0379 Oslo, Norway.
2
Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0379 Oslo, Norway jorrit.enserink@rr-research.no.
3
Section for Biochemistry and Molecular Biology, Faculty of Mathematics and Natural Sciences, University of Oslo, 0371, Norway.

Abstract

Cdk1 (Cdc28 in yeast) is a cyclin-dependent kinase (CDK) essential for cell cycle progression and cell division in normal cells. However, CDK activity also underpins proliferation of tumor cells, making it a relevant study subject. While numerous targets and processes regulated by Cdc28 have been identified, the exact functions of Cdc28 are only partially understood. To further explore the functions of Cdc28, we systematically overexpressed ∼4800 genes in wild-type (WT) cells and in cells with artificially reduced Cdc28 activity. This screen identified 366 genes that, when overexpressed, specifically compromised cell viability under conditions of reduced Cdc28 activity. Consistent with the crucial functions of Cdc28 in cell cycle regulation and chromosome metabolism, most of these genes have functions in the cell cycle, DNA replication, and transcription. However, a substantial number of genes control processes not directly associated with the cell cycle, indicating that Cdc28 may also regulate these processes. Finally, because the dataset was enriched for direct Cdc28 targets, the results from this screen will aid in identifying novel targets and process regulated by Cdc28.

KEYWORDS:

Cdc28; Cdk1; Mutant Screen Report; cell cycle; synthetic lethality

PMID:
28428242
PMCID:
PMC5473755
DOI:
10.1534/g3.117.042317
[Indexed for MEDLINE]
Free PMC Article

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