Cell-cycle regulation is mediated by reversible phosphorylation events - Discuss.

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Oliver Heath                                                                    Corpus Christi College

Cell cycle tutorial 1:

Essay: Cell-cycle regulation is mediated by reversible

             phosphorylation events. Discuss.    

        A cell reproduces by performing an orderly sequence of events in which it duplicates its contents and then divides in two. This cycle of duplication and division, known as cell cycle, is the essential mechanism by which all living cells reproduce. Eucaryotic cells have evolved a complex network of regulatory proteins known as the cell-cycle control system that governs progression through the cell-cycle. The core of this system is an ordered series of biochemical switches that control the main events of the cycle, including DNA replication and the segregation of the replicated chromosomes. A lot of these switches are involved in performing reversible phosphorylation events responsible for mediating cell-cycle regulation.

        The eucaryotic cell-cycle is divided into four sequential phases: G1, S, G2 and M. G1, S and G2 together are called interphase. Cells are released from mitosis into G1 phase, during which there is no DNA replication. The initiation of DNA replication marks the transition from the G1 phase to the period of S phase. The latter lasts until all of the DNA has been replicated. The G2 phase is the period of time that separates the S and M phases and during which the cell has two complete diploid sets of chromosomes. During mitosis, or M phase, cell division occurs and segregates one set of diploid chromosomes to each daughter cell.

The two gap phases (G1 and G2) serve as more than simple time delays to allow cell growth. They also provide time for the cell to monitor the internal and external environment to ensure that conditions are suitable and preparations are complete before the cell commits itself to the major upheavals of S phase and mitosis. If extracellular conditions are unfavourable, for example, cells delay their progress through G1 and may even enter a specialized resting state known as G0 in which they can remain before resuming proliferation. In most cells, there are several points in the cell-cycle called checkpoints at which the cycle can be arrested if previous events have not been completed. Commitment to chromosome replication, for example, in occurs in G1 at a checkpoint called START in yeast cells and restriction point in animal cells. Commitment to mitotic division occurs at the end of G2. At this checkpoint, entry into mitosis is prevented, for example, when DNA replication is not complete. In the same way, chromosome separation in mitosis is delayed if some chromosomes are not properly attached to the mitotic spindle. But what is the molecular basis of this regulation?

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The existence of different regulators at different stages of the cell cycle was revealed by early experiments, performed in yeast that fused together cells in different stages of the cycle. Fusion of the plasma membranes generates a hybrid cell called a heterokaryon that contains two nuclei in a common cytoplasm. The results can be summarized as follows:

When a cell in S phase is fused with a cell in G1, both nuclei in the heterokaryon replicate DNA. This suggests that the cytoplasm of the S phase cell ...

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