Lecture 38 – The Cell Cycle andApoptosis November 27, 2013
The Cell Cycle
• Most of the cells in the body are not dividing, e.g. muscles, nerves, they are in G 0
• Two exceptions are the skin, the gut
• People have found that cells not normally dividing can be induced to divide.
Studying Cell division
• DNAsynthesis, once it starts, is not a smooth rate, there are faster periods and slower periods.
• Rao and Johnson used the Sendai Virus to fuse cells in different phases, S, G etc. 1hey used
techniques like radioactive thymidine to identify the phase of cells
◦ G ad1ed to mitotic cells: G mate1ial started to condense too.
◦ S added to mitotic cells: S material also condensed, but because replicating DNAis
especially sensitive to damage, the result was condensed “pulverized” chromosomes, i.e.
little fragments of condensed chromosome material.
◦ G added to mitotic cells: G material condensed
• Another experiment involved injecting the cytoplasm of cells in different phases into
unfertilized Xenopus embryos to see if it caused the embryos to mature and divide,
◦ Isolated from the cytoplasm was a protein known as Mitosis Promoting Factor (MPK,
originally maturation promoting factor), every time the cell was undergoing mitosis, this
factor increased in concentration.
◦ MPF is composed of two subunits, one has kinase activity, the other is a protein called
cyclin, which varied its concentration in the cytoplasm on a “cyclic” basis.
◦ Cyclin activates the kinase subunit.
◦ Kinases that phosphorylate threonine and serine were also found in the cytoplasm, that
remain at constant levels
◦ As cyclin levels would increase in the cytoplasm, these kinase subunits binds to the cyclin
creating active MPF, thus, Cyclin helps trigger mitosis.
◦ Along with cyclin that stimulates mitosis, a cyclin was found that stimulates entry into the S
phase. Thus there are Mitotic Cyclins and G Cycli1s.
◦ Each of these cyclins has its own Kinases, generically called Cell cycle dependent kinases
1. cdc2 in its in inactive form binds to a Tyrosine-P, a Threonine-P, and Cyclin.
2. Another gene, cdc25, removes the tyrosine-P, activating the cdc2/cyclin complex 3. This stimulates mitosis
4. Afterwards, threonine-P and cyclin dissociate from the cdc2, i.e. complex is degraded.
• An example is ubiquination