• The cells remain metabolically active.
• They usually grow in size, assume particular shape and come
to have a particular function. The phenomenon is called cell
differentiation. Hence, this phase may be temporary or
permanent.
Regulation of cell cycle
• a cell’s ‘decision’ to divide or not is of crucial importance
to the organism. When regulatory mechanisms that limit
cell division are defective and cells undergo unregulated
division, the result is catastrophic– cancer.• The molecular events that control the cell cycle are ordered
and directional; that is, each process occurs in a sequential
fashion and it is impossible to “reverse” the cycle.
Role of cyclins and cDKs
• Two key classes of regulatory molecules, cyclins and cyclin-
dependent protein kinases (CDKs), determine a cell’s
progress through the cell cycle.
• Cyclins are proteins that activate protein kinases to regulate
eukaryotic cell cycle.
• Cyclins form the regulatory subunits and CDKs form the
catalytic subunits of an activated heterodimer.
• Cyclins have no catalytic activity and CDKs are inactive in the
absence of partner cyclin.
• When activated by a bound cyclin, CDKs perform a common
biochemical reaction called phosphorylation that activates
or inactivates target proteins to orchestrate the co-ordinated
entry into the next phase of the cell cycle.
• Different cyclin-CDK combinations determine the downstream
targeted proteins.
• CDKs are constitutively expressed in cells whereas cyclins are
synthesised at specific stages of the cell cycle, in response to
various molecular signals.
general mechanism of cyclin-cDK
interaction
• upon receiving a pro-mitotic extracellular signal, G 1 cyclin-
CDK complexes become active to prepare the cell for S
phase, promoting the expression of transcription factors that
in turn promote the expression of S cyclins and of enzymes
required for DNa replication. The G 1 cyclin-CDK complexes
also promote the degradation of molecules that function as
S phase inhibitors.
• active S cyclin-CDK complexes phosphorylate proteins
that make up the pre-replication complexes assembled
during G 1 phase.
• The phosphorylation serves two purposes: to activate each
already-assembled pre-replication complex, and to prevent
new complexes from forming.
• This ensures that every portion of the cell’s genome will be
replicated once and only once.
• Mitotic cyclin-CDK complexes which are synthesised
but are inactivated during S and G 2 phases promote the
initiation of mitosis by stimulating downstream proteins
involved in chromosome condensation and mitotic spindle
assembly.