Re: What are the main aspects of cell cycle regulation?

The cell cycle is a term for the life of a cell through one cell division 
and all of the mechanisms and processes, which are required for that 
division.  This cycle is broken into various phases which are strictly 
controlled in an order-dependant fashion.  Interphase is where DNA 
replication and growth of the cell occurs, M phase (Mitosis) is where the 
duplicated chromosomes are partitioned, and cytokenisis is when the cell 
divides into two independent entities.  Because of the tremendous importance 
of having a full and correct copy of the genome on survival, a majority of 
the cell cycle mechanisms are devoted DNA synthesis (S phase) and 
partitioning (M phase). There are several "main" aspects to cell cycle 
regulation, and most of the cell cycle control field is very new.  (the most 
important regulators were characterized in 1989)

There are several main aspects of cell cycle:

1) Regulation of DNA synthesis (S phase):

	This is a very interesting topic that is actively being researched.  
When a cell "decides" to replicate its DNA the cell has been energetically 
"committed" to cell division.  Several interesting aspects involve signals 
(hormones), for example, which induce replication by the expression 
transcription of proteins required for replication.  Also, it might be 
interesting to describe how these signals are used to "open up" the DNA (and 
reorganization of nucleosomes) and allow the helicases to unwind. This field 
has a great deal of relevance to cancer, where in many tumor cells the 
control mechanisms which inhibit DNA synthesis have been altered. 

2) Entry and Exit of M phase:

M phase (Mitosis) is induced by MPF (Maturation Promoting Factor).  MPF is a 
heterodimer of two proteins:  Cdc2 and Cyclin B. Cdc2 is a kinase which 
phosphorylates other major proteins involved in regulation and execution of 
cell division.  Cdc2, however, requires cyclin B to be active,  but, the 
abundance/expression/degradation of cyblin B is tightly coordinated with the 
cell cycle.

	A.  ENTRY:  The expression of cyclin B is drastically induced upon 
entry into M-phase.  It has been shown that M phase entry (prophase) 
requires MPF activation (cyclinB+cdc2).  MPF is not only regulated by cyclin 
B availability, but also by the phosphorylation state of cdc2.  (which is 
regulated by other kinases and phosphatases- wee1 and cdc25, respectively)
Therefore, MPF activity is induced, and, in turn prophase (chromosome 
condensation) followed my metaphase (spindle formation and chromosome 
alignment along metaphase plate) occurs.

	B.  EXIT:  Once the duplicated chromosomes have aligned in the midline 
of the cell and the bipolar spindle apparatus is fully formed, the cells 
will only proceed to anaphase unless MPF is inactivated.  The process by 
which MPF is inactivated is by the destruction of cyclin B by Ubiquitin-
mediated proteolysis.  This is a highly specific mechanism where cyclin B is 
"tagged" by Ubiquitin molecules and then targeted by this tag to a large 
complex that cleaves the protein called the proteosome.  On exciting area of 
research, involves the regulation of the complex which tags the cyclin B 
with the Ubiquitin, called the Anaphase Promoting Complex (APC).  Actually, 
it has recently been found that cyclin B is not, in fact, the protein which 
determines the onset of anaphase, but "other" proteins that are also 
degraded by the same APC machinery.

3)  "CHECKPOINTS":  The regulation of the cell cycle is a tightly controlled 
process, not only does cell division require a great deal of energy, but 
faulty cell division and chromosome separation could be fatal.  Therefore, 
the cell has devised various "checkpoint" mechanisms to ensure that each 
step of the cell cycle has been executed correctly before the next stage 
will begin.  There are several critical transitions during the cell cycle 
which are monitored:

	A) DNA synthesis:  It has been shown, for example, that adding 
inhibitors of DNA synthesis or UV light (which fragments the DNA by creating 
thymidine dimers) to a cell in S phase will arrest the cell until the 
inhibitor is removed or the DNA damage is repaired, respectively.  

	B) Spindle checkpoint:  During metaphase of mitosis the duplicated 
chromosomes are aligned along the metaphase plate at the midline of the cell 
by the spindle apparatus.  The spindle is made of filamentous proteins 
called mirotubules that attach by their + ends (fast growing ends) to the 
chromosomes at the kinetochore.  The kinetochore is a protein complex which 
is bound on each side of each chromosome copy.  The kinetochore is situated 
at the centromere of the chromosome.  The microtubules of the spindle attach 
to the kinetochores and orient the chromosomes along the metaphase plate.  
This process is crucial for the correct alignment of the DNA so, that one 
copy of each chromosome is partitioned to the poles during anaphase.  
It has been shown that adding chemicals which disrupt microtubules to cells 
that are in M phase will arrest the cell in m phase.  Also, it has been 
shown that creating one unattached kinetochore by breaking the microtubule 
it is attached to by a laser will induce a metaphase arrest. 

A good review of cell cycle control can be found in the major biochemistry 
and cell biology college textbooks
Biochemistry by Streyer or Voet are good examples
And, Molecular Biology of the Cell is an excellent textbook.