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The Regulation of Cell Cycle

BY: Medha Hegde | Category: Biology | Submitted: 2012-12-06 19:45:06
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Article Summary: "The somatic cell cycle also contains 'Gap' phases recognized as G1, which links the end of M phase to beginning of S phase in the next cycle and G2, which set apart the S and M phases. On the basis of environmental and developmental signals cells in G1 may briefly or permanently depart the cell cycle and enter a detained phase k.."


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Each cell is the result of a cell cycle. The cell cycle is the cycle of events comprising of growth and division of a cell. Proliferation of Cells is controlled accurately by the cell division apparatus, which makes sure that cells divide only at suitable times and the vital components are replicated with proper reliability. The essential mechanisms leading the cell division arose early on in the eukaryotic evolution and are greatly conserved. A characteristic somatic cell cycle can be categorised into 4 orderly phases G1, S, G2 and M phase. The cycle comprises of precise duplication of the genome during the DNA synthesis phase (S phase) and separation of entire set of chromosomes to each of the daughter cells in Mitotic (M) phase. The somatic cell cycle also contains 'Gap' phases recognized as G1, which links the end of M phase to beginning of S phase in the next cycle and G2, which set apart the S and M phases. On the basis of environmental and developmental signals cells in G1 may briefly or permanently depart the cell cycle and enter a detained phase known as G0.
Important components involved in cell cycle regulation.

Cyclin-Dependent Protein Kinase (Cdks) - Cdks are the enzymes that join the phosphate groups (negatively charged) to other molecules in a mechanism called phosphorylation. By phosphorylation, Cdks indicate the cell that it is prepared to move to the next stage of the cell cycle. Cdks are dependent on another group of regulatory proteins called Cyclins. Cyclins combine with Cdks, activating it to phosphorylate other molecules.

Cyclins - they are named so since they go through a regular cycle of synthesis and degradation during cell division. cyclins function as an activating protein and join to Cdks forming a cyclin-Cdk complex. This complex then functions as a signal to the cell to pass to the next phase of the cell cycle. Finally, the cyclin degrades, deactivating the Cdk, thus signalling exit from a particular phase. There are 2 classes of cyclins, G1 cyclins and mitotic cyclins.

E2F Transcriptional factors - A group of helix-loop transcription factors that control expression of a various genes concerned with the cell cycle regulation. They play a key function during the G1to S conversion in plant and mammalian cell cycle.

Retinoblastoma protein (pRb) - It is a tumor suppressor protein that is non-functional in various major cancers. One function of pRb is to put off excessive cell growth by inhibiting cell cycle succession until a cell is ready to divide.

Overview of regulation of cell cycle
The cyclins join with CDK4/CDK6 and must be there in sufficient amounts for the cell to progress through the cell cycle. Cyclin D, CDK complexes act on the retinoblastoma protein (pRb) which is a powerful growth inhibitory molecule. The pRb stops the cell cycle by binding to, and blocking the activity of another protein E2F. E2F is required to turn on many genes involved in cell cycle progression. Active cyclin D CDK complexes phosphorylate and inactivate pRb which leads to the release of E2F. E2F is then free to function and to drive cells through the cell cycle.

At the beginning of the cell cycle levels of G1 cyclins rise and bind to their CDk's, these causes the cells to prepare the chromosomes for replication. Cyclin A binds to CDK2 and E2F forming a protein known as S phase promoting factor (SPF). This SPF enters the nucleus and organizes the cells to replicate its DNA. Mitotic cyclins such as cyclin B complex with CDK2 forming an M phase promoting factor (MPF)which initiates the assembly of the mitotic spindle, breakdown of the nuclear envelop and condensation of the chromosomes. At this point the MPF activates the anaphase promoting complex (APC). This protein induces anaphase by allowing sister chromatids to separate and degrade cyclin B, which induces the completion of mitosis, turns on the synthesis of G1 cyclins for the start of the next cycle and enables DNA replication before the start of the next mitosis. The cell cycle also contains inhibitory proteins like p21, p27 and they stop cell cycle in G1 phase, by binding to, and inactivating, cyclin-CDK complexes. The cell cycle also contains sensors to stop progression if something has gone wrong. These include DNA damage checkpoints and spindle check points. If the damage cannot be repaired the cell will undergo apoptosis (the programmed cell death).

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