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 followsG1/ S transition phase = G1/S cyclins = G1/S CDK
S Phase = S cyclins = S-CDK
M Phase = M cyclins = M-CDK

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 due
to 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 rereplication of DNA or repetition of S-Phase. Thus, S-Phase happens only once per cell cycle. MCDK 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.