Thursday, December 25, 2008

CELL CYCLE



A eukaryotic cell undergoes alternate phases of division and non-division. The sequences of events occurring from the completion of one division to the next division form one cell cycle. The stage, or the interval, between two consecutive mitotic divisions is the interphase. Therefore, a cell cycle can be considered as interphase + mitosis. The interphase is metabolically very dynamic and is further divided into S-phase, Gl, and G2 phase. The period between M-phase and S-phase is called G1; that between S and M is G2. A cell cannot divide into two, the two into four, etc., unless two processes alternate: doubling of its genome (DNA) in S-phase (synthesis phase) of the cell cycle and halving of that genome during mitosis (M-phase).

Stages of Cell Growth:

1. G1 phase: primary growth phase. Cell does its housekeeping activities. 
2. S-phase: DNA replication. 
3. G2 phase: chromosome condensation, cell organelle replication. 
4. M-phase: mitosis (nuclear division) (prophase, metaphase, anaphase, and telophase). 
5. C phase: cytokinesis (cytoplasmic division), daughter cells form.

Interphase is the longest stage of the cell cycle. Human cells contain 46 chromosomes during the Gl stage of interphase. This is doubled to 92 during the S stage of interphase. 

A typical cell takes about 16 hours to complete the cell cycle. The actual process of cell division or mitosis occupies only a small part of this cycle, approximately one hour. The lengths of Sand G2 are almost equal in all cell types, but the length of the Gl phase varies considerably between cells.

Normally the cells at G1 phase can follow either of the two paths. The cell after the cell division may withdraw from the cell cycle and enter into a resting phase called the Go phase, or it can enter into the G1 phase of the cell cycle. Cells in the Go phase are viable and metabolically active but can be stimulated to enter into the G1 phase at any time and start the cell cycle again. Often, Go cells are terminally differentiated: they will never re-enter the cell cycle but instead will carry out their function in the organism until they die.

For other cells, Go can be followed by re-entry into the cell cycle. Most of the lymphocytes in human blood are in Go. However, with proper stimulation, such as encountering the appropriate antigen, they can be stimulated to re-enter the cell cycle (at G1) and proceed onto new rounds of alternating S phases and mitosis. Go represents not simply the absence of signals for mitosis but an active repression of the genes needed for mitosis. Cancer cells cannot enter Go and are destined to repeat the cell cycle indefinitely. 

Regulation of the Cell Cycle

The cell cycles in almost all eukaryotic cells are essentially the same with minor variations in the duration of each phase. There are some proteins in the cytoplasm that control and coordinate the passage of a cell in the correct order through the cell cycle. The major proteins involved in the regulation are called cyelins. There are three groups:

G1 cyelins S-
phase cyelins M-
phase cyelins

The levels of these cyclins in the cell rise and fall with the stages of the cell cycle. The group of enzymes, Cyelin-dependent kinase (CDKs), phosphorylate cyclins. Again, there are three groups of CDKs:

G1 CDKs
S-phase CDKs M-
phase CDKs

Their levels in the cell remain fairly stable, but each must bind to the appropriate cyclin in order to be activated. The levels of cyclins always fluctuate in the cells. The CDKs add phosphate groups to a variety of protein substrates that control processes in the cell cycle.

The third group of proteins involved in the regulation of cell cycle is anaphase-promoting complex (APC) and other proteolytic enzymes. The APC triggers the events leading to destruction of the cohesin (a protein that joins the sister chromatids), thus allowing the sister chromatids to separate. It also degrades the mitotic (M-phase) cyclins. 

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