Generic Cell Cycle Model

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Biological background

Cell cycle is the period of time that is needed for a cell to double its genetic content and distribute it to two daughter cells. In most cells this time is coupled to the duplication of other cell contents and cells can divide only after doubling their size ( Sveiczer et al., 1996 ). A typical cell goes through a precise DNA replication and mitosis (doubling and distributing genetic information) while its ribosome number and cell mass approximately doubles. Usually the slower process is the duplication of cell mass, which creates special phases into the cell cycle. Between S-phase (DNA replication) and M-phase (mitosis) growing, genetically resting phases are incorporated, G1 and G2. So the typical somatic eukaryotic cell cycle is ordered in G1, S, G2 and M-phases. Special checkpoints of the cell cycle coordinate cell growth with the DNA cycle , the cells has to reach a critical size to start S phase and has to complete DNA replication and might need to reach another critical size to initiate mitosis. Before subsequent S-phase the proper finish of M-phase is also checked. In homeostasis cell growth and the DNA cycle balances each other with the help of extended G1 and G2 phases, so individual cell cycle times in a population of cells will be equal to the mass doubling time (MDT) of the population.

The eukaryotic cell cycle engine
The organization of these complicated tasks is mastered by a complicated molecular regulatory network. The main components of this network are cyclin dependent protein kinases (Cdk), which activate crucial cell cycle steps by phosphorylation. Cdk's are active only if they are bound by a cyclin regulatory molecule. Yeasts have only one Cdk type that can induce S or M-phase depending on which cyclin binding partner activated the Cdk. Because Cdk's are always present in excess the comings and goings of cyclins drive cell cycle transitions ( Cross et al., 2002 ). Cdk/cyclin complexes also can be regulated by inhibitory phosphoryation, mostly in G2 by Wee1 kinase and by stoichometric Cdk inhibitor (CKI) binding, mostly in G1 ( Nurse, 1985 ). It has been proposed a long time ago ( Nurse, 1990 ) that the M-phase control mechanism is generic among these cells. Now we know that not only the mitotic transition regulation but most of the major steps of cell cycle seem to be universal in eukaryotes. Here we investigate all the major modules of the eukaryotic cell cycle regulatory networks and show the universality and uniqueness of subsystems between different organisms.