Friday, December 26, 2008

The Important Steps in the Cell Cycle

A rising level of G1 cyelins signals the cell to prepare the chromosomes for replication. A rising level of S-phase promoting factor (SPF) prepares the cell to enter S-.phase and duplicate its DNA (and its centrioles). As DNA replication continues, one of the cyclins shared by G1 and S-phase CDKs (cyclin E) is destroyed and the level of mitotic cyclins begins to rise (in G2).

M-phase promoting factor (the complex of mitotic cyclins with M-phase CDK) initiates the assembly of the mitotic spindle, breakdown of the nuclear envelope, and condensation of the chromosomes.

These events take the cell to the metaphase of mitosis.

At this point, the M-phase promoting factor activates the anaphase promoting complex (APC), which allows the sister chromatids at the metaphase plate to separate and move to the poles (= anaphase), completing mitosis: It destroys the M-phase cyclins. It also turns on synthesis of G1 cyclins for the next turn of the cycle and degrades geminin, a protein that has kept the freshly-synthesized DNA in S-phase from being re-replicated before mitosis.

Checkpoints: Quality Control of the Cell Cycle

The cell has several systems for interrupting the cell cycle if something goes wrong. There are some points in the cell cycle where the cell can check the sequence of activities related to its replication. These points are known as checkpoints. The following are the important checkpoints in the cell cycle, which monitor the healthy progress of cell division:
DNA damage checkpoints:

These sense DNA damage before the cell enters S-phase (a G1 checkpoint), during S-phase, and after DNA replication (a Gz checkpoint). The cell seems to monitor the presence of okazaki fragments on the lagging strand during DNA replication. The cell is not permitted to proceed in the cell cycle until these have disappeared.

Spindle checkpoints:

These are the final checkpoints also known as M-phase checkpoints. They detect any failure of spindle fibers to attach to kinetochores and arrest the cell in metaphase (M checkpoint). They monitor the alignment and detect improper alignment of the spindle itself and block cytokinesis. If the damage caused to the DNA is irreparable, it triggers the process of apoptosis or cell death.

All the checkpoints examined require the services of a complex of proteins. Mutations in the genes encoding have been associated with cancer; that is, they are oncogenes. This should not be surprising since checkpoint failures allow the cell to continue dividing despite damage to its integrity.

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