Okinawa Institute of Science and Technology


Mitsuhiro Yanagida Unit
G0 Cell Unit


		<Links> OIST G0 Cell Unit Kyoto University GRADUATE SCHOOL OF BIOSTUDIES, KYOTO UNIVERSITY

< Abstract >

Cell growth and multiplication are a central problem in biology. Our proposal is focused on the adaptation strategy for cell cycle arrest by nutrient starvation and the re-initiation of growth when starved cells are returned to a rich medium. We want to investigate the molecular-switch problem: how cells can control and execute an arrest at the G0-like differentiated state, and how cell growth and division resumes when the nutritional environment improves. Understanding the transition from the G0-arrest to growing states at the molecular level is the purpose of this proposal. We will employ post-genomic methods that produce quantitative information about individual genes in combination with genetic approaches using fission yeast as a model organism. If clear mechanistic principle emerges from these studies, we plan to extend the knowledge obtained to mammalian cell systems, using sets of conserved gene products. We aim to identify and characterize genes that command the G0-like cell stage or the return to growth. Our proposal has implications in broad research areas: cell cycle control, developmental biology, cancer research, chromosome biology, genome science and systems biology.

< Research Goals >

We want to solve the “molecular-switch Eproblem how cells can decide to arrest at the G0-like non-dividing state and re-start cell division under the change of nutritional environment.


< Strategy >
We use the fission yeast as a model organism, all the ∼4900 genes of which has been assigned from the whole genome. We employ integrated post-genomic approaches (microarray hybridization, proteomic analysis) in combination with genetics and molecular cell biological methods. Later, we plan comparative studies using vertebrate cells.

< Common properties with quiescent G0 cells >

Cells can sense the environmental (nutrient) signal to start or stop division. Cell division cycle kinase (CDK) is properly regulated. Cell shape is largely changed. Chromosomes are in the G1-state (pre-replicative). Protein synthesis is largely shut down to a low maintenance mode. Ribosome biosynthesis essentially ceases.

< Genes which we will focus on >

Functionally unknown but evolutionarily conserved candidates for the regulators.



< Expected Outcome >

Any essential progress in a basic “Cell growth and arrest Eproblem has certain impacton life science and will be welcome by human society. Control of cell growth has many application areas in medicine and biotechnology.


< References >

A nitrogen starvation-induced dormant G0 state in fission yeast: the establishment from uncommitted G1 state and its delay for return to proliferation. Su SS, Tanaka Y, Samejima I, Tanaka K, Yanagida M. J Cell Sci. 1996 Jun;109 ( Pt 6):1347-57. Cnd2 has dual roles in mitotic condensation and interphase. Aono N, Sutani T, Tomonaga T, Mochida S, Yanagida M. Nature. 2002 May 9;417(6885):197-202. Regulation of checkpoint kinases through dynamic interaction with Crb2. Mochida S, Esashi F, Aono N, Tamai K, O’Connell MJ, Yanagida M. EMBO J. 2004 Jan 28;23(2):418-28 Cleavage of Cohesin by Separase in Interphase Is Required for DNARepair. Nagao K, Adachi Y, Yanagida M. Nature. In press