CELL DIVISION

Eukaryotic Cell Cycle and Its

Regulation
 The Eukaryotic Cell Cycle
• The division cycle of most cells consists of four coordinated
processes: cell growth, DNA replication, distribution of the
duplicated chromosomes to daughter cells, and cell division.

• The cell cycle in eukaryotes is a complex process and consists of

four discrete phases: M, G1, S, G2

• Although cell growth is usually a continuous process, DNA is

synthesized during only one phase (S) of the cell cycle, and the
replicated chromosomes are then distributed to daughter nuclei by
a complex series of events followed by cell division.

• Movement between these stages of the cell cycle is controlled by a

conserved regulatory apparatus (Cyclins and Cyclin dependent
kinases, checkpoints etc.), which not only coordinates the
different events of the cell cycle but also links the cell cycle with
extracellular signals that control cell proliferation.
 Phases of the Eukaryotic Cell Cycle
• The cell cycle is divided into two basic parts: mitosis and interphase.

• A typical eukaryotic cell cycle divide approximately every 24 hours.

• Mitosis (nuclear division) is the most dramatic stage of the cell cycle,
corresponding to the separation of daughter chromosomes and usually
ending with cell division (cytokinesis).

• Mitosis and cytokinesis last only about an hour, so approximately 95%

of the cell cycle is spent in interphase-the period between mitoses.

• During interphase, the chromosomes are decondensed and distributed

throughout the nucleus, so the nucleus appears morphologically uniform.

• At the molecular level, interphase is the time during which both cell
growth and DNA replication occur in an orderly manner in preparation for
cell division.
The timing of DNA synthesis divides the cycle of eukaryotic
cells into four discrete phases

The M phase: mitosis takes place, which is usually

followed by cytokinesis. It is followed by G1 phase.

G1 phase (Gap 1): it is the interval (gap) between mitosis

and initiation of DNA replication. During G1 the cell is
metabolically active and continuously grows but does not
replicate its DNA. G1 is followed by S Phase.

S phase (synthesis): during which DNA replication takes

place. It is followed by the G2 Phase.

G2 phase (Gap 2): during which cell growth continues and

proteins are synthesized in preparation for mitosis.
• The duration of these cell cycle phases varies considerably in
different kinds of cells.

• For a typical rapidly proliferating human cell with a total cycle

time of 24 hours, the G1 phase might last about 11 hours, S phase
about 8 hours, G2 about 4 hours, and M about 1 hour.

• Other types of cells, however, can divide much more rapidly.

Budding yeasts, for example, can progress through all four stages
of the cell cycle in only about 90 minutes.

• In contrast to the rapidly proliferating cells (e.g. embryonic cells),

some cells in adult animals stop dividing altogether (e.g., nerve
cells) and many other cells divide only occasionally, as needed to
replace cells that have been lost because of injury or cell death.

• These cells exit G1 to enter a quiescent stage of the cycle called

G0, where they remain metabolically active but no longer
proliferate unless called on to do so by some extracellular signals.
Cell Cycle Regulation
• In most cells coordination between different phases of the cell cycle is dependent on a series
of cell cycle checkpoints that prevent entry into the next phase of the cell cycle until the
events of the previous phase have been completed.

• Several cell cycle checkpoints function to ensure that incomplete or damaged chromosomes
are not replicated and passed on to daughter cells These checkpoints sense unreplicated or
damaged DNA and coordinate further cell cycle progression with the completion of DNA
replication or repair.

• For example, the checkpoint in G2 prevents the initiation of mitosis until DNA replication is
completed. This G2 checkpoint senses unreplicated DNA, which generates a signal that leads
to cell cycle halt.

• Operation of the G2 checkpoint therefore prevents the initiation of M phase before completion
of S phase, so cells remain in G2 until the genome has been completely replicated.

• Cell cycle arrest at the G1, S, and G2 checkpoints is mediated by two related protein
kinases, designated ATM (ataxia-telangiectasia mutated) and ATR (ATM- and
Rad3-Related), that recognize damaged or unreplicated DNA and are activated in
response to DNA damage.
 Role of cyclin-cdk in cell cycle regulation
• Cell cycle phases of all eukaryotes is controlled by a
conserved set of protein kinases (e.g. cdk- cyclin
dependent kinases) and proteins (i.e. Cyclins – periodic
proteins; Tim Hunt et al. identified Cyclin A and B),
which are responsible for triggering the major cell
cycle transitions.

• Cdk1 and cyclin B constitute the maturation

promoting factor (MPF).

• In somatic cells, MPF induces entry into M phase of

the mitotic cycle. MPF act as a general regulator of the
transition from G2 to M.
 Cyclin dependent kinases can add phosphates to other
proteins. They serve as “master control” molecules
functioning in conjunction with proteins called cyclins.

Cyclins bind to these kinases (creating cyclin-dependent

kinases) activating them at appropriate times during the cell
cycle.

Activated kinases then phosphorylate other target proteins

that regulate the progress of the cell cycle.

The cell cycle contains at least three major checkpoints,

where the processes culminating in normal mitosis are
monitored, or “checked,” by these master control molecules
(cdk-cyclin complexes) before the next stage of the cycle
commences.