We all have memorized (excuse me, I meant learned) what goes on during prophase, metaphase, anaphase, and telophase, but do you really know how the cell makes all of this happen?  Why is cell cycle control important?  Cancer is one answer.  The loss of control leads to such serious problems and understanding the mechanisms that work (or fail) help researchers to discover cures or treatments.  This section does not deal with the mechanisms of mitosis, but instead deals with mechanisms the influence mitosis and help accomplish the proliferation of correct copies of cells (free of errors), the important goal of mitosis for a cell.  Experiments have shown that cells will either halt the cell cycle and wait for corrections to be made or move towards a pathway for suicide (apoptosis) when abnormalities like the failure of sister chromatids to separate occur.  How do we know this and other relevant information?  Keep on reading...

Yeasts, clams, frogs, sea urchins have been studied to help us better understand human cell cycle control (without having to do unnecessary experiements on your grandma).  Here are some of the results of the past 20 years.

1) The cytoplasm was taken out of immature frog eggs that were dividing and placed in dividing eggs.  They started dividing!  This lead to the finding of a protein kinase called maturation promoting factor (MPF).  As mentioned, MPF induces non-dividing frog eggs to divide (entry into the M phase).  MPF activity fluctuates.  It rises before division and then sharply drops.
Frog MPF was purified to 2 protein complexes, 32kD (protein kinase active site and homologous to yeast cdc2 protein kinase) and 45kD (a cyclin required for protein kinase activity).

2) Sea urchins help us discover a new protein that is made within 10 minutes of fertilization and then disappears afterwards.  The protein is CYCLIN.  You'll here plenty about cyclin, just you wait.

3) Cell cycle mutant fission yeast were screened at high temperatures.  Now we know about the cell division cycle 2 (cdc2) gene which encodes for protein 34 (p34) kinase.  Antibodies can be used to recognize the yeast p34 kinase.

1)  The association of cdc2 kinase with cyclins and their rise and fall through the cell cycle
2)  The study of transforming viruses:
Oncogenes (originating from protooncogenes) are from too much cell division.  Reduced GTPase activity or increased exchange reaction will are characteristic of this.  An oncogene present will be dominant when heterozygous.
3)  Tumor suppressor genes are inherited.  They tell the cell not to divide.  An abnormality will arise when the tumor suppressor gene is heterozygous with a normal gene that is then mutated or replaced by mitotic homologous recombination. 

The retinoblastoma gene product (pRb) binds to more than 30 different proteins.  One class of proteins are the E2F transcription factors.  They regulate expression of various enzymes involved in dNTP and DNA synthesis.  If pRb is bound to the E2F, replication is blocked.  pRb is reversibly phosphorylated by cdc2 kinase.  This is the last guard so that the cell won't enter the S phase.

The p53 tumor suppressor gene encodes for p53, a transcription factor that binds to the gene for p21.  p21 is the inhibitor for the cyclin E-cdk2 complex.  This stops the cell cycle processes so repairs can be made or apoptosis can begin.

Another known control is the prevention of microtubules from working.  Mitotic Arrest Deficient (MAD) genes continue despite mutations.  When cell cycles go wrong (sounds like a show that Fox would put on sporadically), MAD will be present in larger amounts.  The MAD gene product senses mechanical tension of pulling chromosomes apart towards their respective poles.  A lack of separation will stop the cell cycle and lead to apoptosis.