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Msg #8884: pletchermrj (yourmail@gmail.com) ,  2012-02-09 21:46:05.644486+01
 Many of the most important discoveries about the mechanisms that control events of the cell cycle

It should seem obvious that the processes that drive a cell through the cell cycle must be highly regulated so as to ensure that the resultant daughter cells are viable and each contains the complement of DNA found in the original parental cell. There are many "parts" to the systems that control the transit through a eukaryotic cell cycle. These "parts" include mechanisms to control the timing of events so that each individual process is turned on and off at the appropriate time, mechanisms to initiate each event in the correct order and to also ensure that each event is triggered only once per cell cycle, controls to ensure events occur in a linear, irreversible direction, redundancy, or back-ups to ensure the cycle functions properly even in the context of some malfunctioning parts, and systems that are adaptable so that cell cycle events can be modified in the context of different cell types and/or environmental conditions. Many of the most important discoveries about the mechanisms that control events of the cell cycle were elucidated using yeasts which are single cell eukaryotes. By analysis of various mutants that inactivated genes encoding essential components of cell cycle control systems in yeast many important control genes were identified. These genes were identified as cell division cycle genes or cdc genes. Thus, many cell cycle control genes in mammalian cells are also called cdc genes. Much of the control of the progression through the phases of a cell cycle are exerted at checkpoints. There are many such checkpoints but the two most critical are those that occur near the end of G1 prior to S-phase entry and those near the end of G2 prior to mitosis. As indicated above, there is the need for cell cycle control mechanisms to exert their influences at specific times during each transit through a cell cycle. The heart of this timing control is the responsibility of a family of protein kinases that are called cyclin-dependent kinases, CDKs. The kinase activity of these enzymes rises and falls as the cell progresses through a cell cycle. Different CDKs operate at different points in the cell cycle. As would be expected, the oscillating changes in the activity of CDKs leads to oscillating changes in the phosphorylation of various intracellular proteins. These phosphorylations alter the activity of the modified proteins which then effect changes in events of the cell cycle. The cyclical activity of each CDK is controlled by a complex series of proteins, the most important of which are the cyclins, hence the name of the enzymes as cyclin-dependent kinases. The CDKs are absolutely dependent upon their interaction with the cyclins for activity. Unless they are tightly bound CDKs have no kinase activity. The cyclins were originally idenitified because they undergo a cycle of synthesis and degradation at specific points in each cell cycle. Thus, whereas the levels of the various CDKs remain fairly constant throughout the cell cycle, their activities changes in concert with the fluctuations of the cyclins. Four different classes of cyclins have been defined on the basis of the stage of the cell cycle in which they bind and activate CDKs. These four classes are G1-cyclins, G1/S-cyclins, S-cyclins, and M-cyclins. The cyclin nomenclature and associated CDK in mammalian cells are listed in the following Table.
 
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