The Cell Cycle

Index to this page
A eukaryotic cell cannot divide into two, the two into four, etc. unless two processes alternate:

The period between M and S is called G1; that between S and M is G2.


So, the cell cycle consists of: When a cell is in any phase of the cell cycle other than mitosis, it is often said to be in interphase.

Control of the Cell Cycle

The passage of a cell through the cell cycle is controlled by proteins in the cytoplasm. Among the main players in animal cells are:

Steps in the cycle

Some cells deliberately cut the cell cycle short allowing repeated S phases without completing mitosis and/or cytokinesis. This is called endoreplication and is described on a separate page. Link to it.

Meiosis and the Cell Cycle

The special behavior of the chromosomes in meiosis I requires some special controls. Nonetheless, passage through the cell cycle in meiosis I (as well as meiosis II, which is essentially a mitotic division) uses many of the same players, e.g., MPF and APC. (In fact, MPF is also called maturation-promoting factor for its role in meiosis I and II of developing oocytes.

Checkpoints: Quality Control of the Cell Cycle

The cell has several systems for interrupting the cell cycle if something goes wrong.

All the checkpoints examined require the services of a complex of proteins. Mutations in the genes encoding some of these 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.

Examples

p53

The p53 protein senses DNA damage and can halt progression of the cell cycle in G1 (by blocking the activity of Cdk2). Both copies of the p53 gene must be mutated for this to fail so mutations in p53 are recessive, and p53 qualifies as a tumor suppressor gene.
Further discussion of tumor suppressor genes and p53.

The p53 protein is also a key player in apoptosis, forcing "bad" cells to commit suicide. So if the cell has only mutant versions of the protein, it can live on — perhaps developing into a cancer. More than half of all human cancers do, in fact, harbor p53 mutations and have no functioning p53 protein.

A genetically-engineered adenovirus, called ONYX-015, can only replicate in human cells lacking p53. Thus it infects, replicates, and ultimately kills many types of cancer cells in vitro. Clinical trials are now proceeding to see if injections of ONYX-015 can shrink a variety of types of cancers in human patients. (You will find that the human gene is variously designated as P53, TP53 ["tumor protein 53"], and TRP53 ["transformation-related protein 53"])

ATM

ATM (="ataxia telangiectasia mutated") gets its name from a human disease of that name [Link], whose patients — among other things — are at a greatly increased (~100 fold) risk of cancer. The ATM protein is involved in

MAD

MAD (="mitotic arrest deficient") genes (there are two) encode proteins that bind to each kinetochore until a spindle fiber (one microtubule will do) attaches to it. If there is any failure to attach, MAD remains and blocks entry into anaphase (by inhibiting the anaphase-promoting complex).

Link to discussion of chromosome behavior in anaphase.

Mutations in MAD produce a defective protein and failure of the checkpoint. The cell finishes mitosis but produces daughter cells with too many or too few chromosomes, a condition called aneuploidy. More than 90% of human cancer cells are aneuploid.

Infection with the human T-cell lymphotropic virus-1 (HTLV-1) leads to a cancer (ATL = "adult T-cell leukemia/lymphoma") in about 5% of its victims. HTLV-1 encodes a protein, called Tax, that binds to MAD protein causing failure of the spindle checkpoint. The leukemic cells in these patients show many chromosome abnormalities including aneuploidy.

A kinesin that moves the kinetochore to the end of the spindle fiber also seems to be involved in the spindle checkpoint [More].

G0

Many times a cell will leave the cell cycle, temporarily or permanently. It exits the cycle at G1 and enters a stage designated G0 (G zero). A G0 cell is often called "quiescent", but that is probably more a reflection of the interests of the scientists studying the cell cycle than the cell itself. Many G0 cells are anything but quiescent. They are busy carrying out their functions in the organism. e.g., secretion, attacking pathogens.

Often G0 cells are terminally differentiated: they will never reenter the cell cycle but instead will carry out their function in the organism until they die.

For other cells, G0 can be followed by reentry into the cell cycle. Most of the lymphocytes in human blood are in G0. However, with proper stimulation, such as encountering the appropriate antigen [View], they can be stimulated to reenter the cell cycle (at G1) and proceed on to new rounds of alternating S phases and mitosis.

G0 represents not simply the absence of signals for mitosis but an active repression of the genes needed for mitosis. Cancer cells cannot enter G0 and are destined to repeat the cell cycle indefinitely. [More]

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5 April 2014