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CONTROL OF THE CELL CYCLE

Cyclin-dependent kinase (CDK) regulation

The transition from one cell cycle phase to another occurs in an orderly fashion and is regulated by different cellular proteins. Key regulatory proteins are the cyclin-dependent kinases (CDK), a

family of protein kinases that are activated at specific points of the cell cycle by a family of

 proteins called Cyclins. Upon activation, CDK induce downstream processes by

 phosphorylating selected proteins (Morgan 1995; Pines 1995).

CDK protein levels remain stable during the cell cycle, in contrast to cyclins. Cyclin protein

levels rise and fall during the cell cycle and in this way they periodically activate CDK (Evans et

al.1983; Pines 1991). Different cyclins are required at different phases of the cell cycle. During

G1 phase a group of cyclins that are synthesized are called G1 cyclins which activate certain

CDK molecules forming a complex called as G1-CDK . Similarly other cyclins and cyclin  –  

CDk complexes formed are as follows-

G1/ S transition phase = G1/S cyclins = G1/S  –  CDK

S Phase = S cyclins = S-CDK

M Phase = M cyclins = M-CDK

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The three dotted lines in above figure denote the Cell cycle check points. The G1 cyclins are

synthesized by the cell when there are favourable extra-cellular conditions for cell growth with

adequate amount of nutrition, growth factors and mitogens. The G1 cyclins will initiate proper

growth and enlargement of cell, and will ensure progression of cell cycle.

At the first checkpoint, if there is DNA damage the down-stream cyclins are not synthesized and

cell cycle progression gets halted. Similarly after S phase if there is some DNA left unduplicated

or there is some DNA damage during replication process, the M-cyclin synthesis is stopped dueto which the M-CDKs complex are not formed further halting the M-Phase. This check is done

at the second checkpoint i.e. G2/M. In normal course the M-CDK complex prevent re-

replication of DNA or repetition of S-Phase. Thus, S-Phase happens only once per cell cycle. M-

CDK complex helps initiate Cell division/ Mitosis process. The third Checkpoint of cell cycle

exists at the Metaphase-Anaphase transition where the chromosome segregation to opposite

 poles is initiated only if all the spindle fibers get attached to all the chromosomes. This check is

 performed by APC/C protein which is also a kind of CDK.