Cell cycle control (Stephan Geley)

Life is based on cellular replication. For faithful inheritance and maintenance of genetic identity exact replication of the genomic blueprint and its accurate segregation into the dividing daughter cells are mandatory. Cellular replication is controlled by the cell division cycle, a process that responds to extracellular cues and results in two genetically identical daughter cells. An exception is meiosis which results in genetically different gametes. The cell cycle is divided into the actual division or M-phase, including mitosis (nuclear division) and cytokinesis (cellular division), as well as interphase, which consists of G1-, S-, and G2-phase. In all eukaryotes, transitions between these phases are controlled by cyclin dependent kinases (CDKs). Control of G1-phase is essential for committing cells to one round of cellular replication and deregulation of G1-phase is the most common cause of tumorigenesis. Errors in DNA replication during S-phase and chromosome segregation during mitosis cause aneuploidy, a characteristic hall mark of cancer.

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Cell cycle control Project #1: Function and regulation of FZR1
Figure 1: The cell division cycle in somatic cells Figure 2: FZR1 is essential for vertebrate development

Project #2: Function and regulation of Spindly Project #3: Function and regulation of Cyclin-Y dependent kinases
Figure 3: Spindly controls chromosome movements and mitotic checkpoint inactivation Figure 4: CDK16 is required for spermatogenesis

Project #4: Function and regulation of human chromokinesins
Figure 5: Chromokinesins are required for efficient chromosome congression

PhD Training

Our group is embedded in the MCBO (link to MCBO homepage) PhD program and we offer several lectures on basic concepts of cell cycle regulation as well as hands-on courses, including live cell imaging, production of recombinant kinases, advanced DNA cloning technologies and others.

Key Publications

(A complete list of publications may be found here)

Sigl, R., Ploner, C., Shivalingaiah, G., Kofler, R. & Geley, S. (2014). Development of a multipurpose GATEWAY-based lentiviral tetracycline-regulated conditional RNAi system (GLTR). PLoS ONE, 9(5), e97764 PMID: 24841113.

Wandke C, Barisic M, Sigl R, Rauch V, Wolf F, Amaro AC, Tan CH, Pereira AJ, Kutay U, Maiato H, Meraldi P, Geley S (2012). Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis. J Cell Biol. 198 (5): 847-63 PMID: 24841113.

Mikolcevic P, Rainer J, Geley S (2012). Orphan kinases turn eccentric: a new class of cyclin Y-activated, membrane-targeted CDKs. Cell Cycle 11 (20): 3758-68 PMID: 22895054.

Mikolcevic P, Sigl R, Rauch V, Hess MW, Pfaller K, Barisic M, Pelliniemi LJ, Boesl M, Geley S (2012). Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by cyclin Y and is essential for spermatogenesis. Mol Cell Biol. 32 (4): 868-79.PMID: 22184064

Barisic M, Geley S (2011). Spindly switch controls anaphase: spindly and RZZ functions in chromosome attachment and mitotic checkpoint control. Cell Cycle 10(3):449-56.PMID: 21252629

Barisic M, Sohm B, Mikolcevic P, Wandke C, Rauch V, Ringer T, Hess M, Bonn G, Geley S (2010). Spindly/CCDC99 is required for efficient chromosome congression and mitotic checkpoint regulation. Mol Biol Cell 21(12): 1968-81.PMID: 20427577

Sigl R, Wandke C, Rauch V, Kirk J, Hunt T, Geley S (2009). Loss of the mammalian APC/C activator FZR1 shortens G1 and lengthens S phase but has little effect on exit from mitosis. J Cell Sci. 122 (Pt 22): 4208-17.PMID: 19861496

Wolf F, Wandke C, Isenberg N, Geley S (2006). Dose-dependent effects of stable cyclin B1 on progression through mitosis in human cells. EMBO J. 25 (12): 2802-13.PMID: 16724106