CELL CYCLE AND

CELL DEATH
Brian Wasita,dr.,Ph.D
CELL
CYCLE
 CELL CYCLE
PHASES OF THE CELL CYCLE

Prophase, Prometaphase, Metaphase,

Anaphase, Telophase, Cytokinesis
The cell cycle with checkpoints
 M phase

Consists of

1.nuclear division (mitosis) : mediated by a microtubule-based mitotic spindle, which

separates the chromosomes

2.cytoplasmic division (cytokinesis) : mediated by an actin-filament-based contractile ring

Centrosome : the principal microtubule organizing center (MTOC) in most animal cells
duplicated before eucaryotic cell divides to provide one for each of its two daughter cells

Centrosome duplication begins during the S and G2 phases, the duplicated centrosomes
separate and move to opposite sides of the nucleus at the onset of M phase, form the two
poles of the mitotic spindle.

Large membrane-bounded organelles (such as the Golgi apparatus and the endoplasmic
reticulum) break up into many smaller fragments during M phase to ensure their even
distribution into daughter cells during cytokinesis.
The cytoskeleton in M phase.
The mitotic spindle assembles first and
segregates the chromosomes. The
contractile ring assembles and
later divides the cell in two.
 The centrosome cycle of an animal cell.

The centrosome in an interphase cell duplicates to form the two poles of a mitotic spindle. In most animal cells a centriole pair
(shown here as a pair of dark green bars) is associated with the centrosome matrix (light green) that nucleates microtubule
outgrowth. (The volume of centrosome matrix is exaggerated in this diagram for clarity; Figure18-4 gives a more accurate
representation.) Centriole duplication begins in G1 and is completed by G2 (see Figure 18-4). Initially, the two centriole pairs and
associated centrosome matrix remain together as a single complex.
In early M phase this complex separates into two and each centrosome nucleates a radial array of microtubules, called an aster.
The two asters, which initially lie side by side and close to the nuclear envelope, move apart. By late prophase the bundles of polar
microtubules that interact between the two asters preferentially elongate as the two centers move apart along the outside of the
nucleus. In this way a mitotic spindle is rapidly formed. At metaphase the nuclear envelope breaks down, enabling the spindle
microtubules to interact with the chromosomes; at cytokinesis the nuclear envelope re-forms around the two sets of segregated
chromosomes, excluding the centrosomes.
A typical time course for mitosis and cytokinesis (M
phase) in a mammalian cell.
The course of mitosis in a typical animal cell.
The six stages of cell division
Regulation of Cell cycle
 Cell cycle regulator
I.Cyclins and cyclin-dependent kinases
Proteins within cytoplasma that control the cell cycle
Cyclins : the regulatory subunit
CDKs: the catalytic subunit

II.Tumor suppressor genes

1.P53 gene
2.Retinoblastoma gene
(Rb Gene)
Schematic illustration of the role of cyclins, CDKs, and CDKIs in regulating the cell cycle. The shaded
arrows represent the phases of the cell cycle during which specific cyclin-CDK complexes are active. As
illustrated, cyclin D-CDK4, cyclin D-CDK6, and cyclin E-CDK2 regulate the G1-to-S transition by
phosphorylation of the RB protein (pRB). Cyclin A-CDK2 and cyclin A-CDK1 are active in the S phase.
Cyclin B-CDK1 is essential for the G2-to-M transition. Two families of CDK inhibitors can block activity of
CDKs and progression through the cell cycle. The so-called INK4 inhibitors composed of p16, p15, p18,
and p19, act on cyclin D-CDK4 and cyclin D-CDK6. The other family of three inhibitors, p21, p27, and p57,
can inhibit all CDKs.
The role of RB in regulating the G1-S checkpoint of the cell cycle. Hypophosphorylated RB in complex with the E2F transcription
factors binds to DNA, recruits chromatin remodeling factors (histone deacetylases and histone methyltransferases), and inhibits
transcription of genes whose products are required for the S phase of the cell cycle. When RB is phosphorylated by the cyclin
D-CDK4, cyclin D-CDK6, and cyclin E-CDK2 complexes, it releases E2F. The latter then activates transcription of S-phase
genes. The phosphorylation of RB is inhibited by CDKIs, because they inactivate cyclin-CDK complexes. Virtually all cancer
cells show dysregulation of the G1-S checkpoint as a result of mutation in one of four genes that regulate the phosphorylation of
RB; these genes are RB, CDK4, cyclin D, and CDKN2A [p16]. EGF, epidermal growth factor; PDGF, platelet-derived growth
factor.
CELL DEATH
• Necrosis is the major pathway of cell death in many commonly
encountered injuries, such as : ischemia, exposure to toxins,
various infections, and trauma.

• Apoptosis will occur when a cell is deprived of growth factors or

when the cell's DNA or proteins are damaged beyond repair.
 CAUSES OF CELL INJURY

• Oxygen Deprivation

• Chemical Agents

• Infectious Agents

• Immunologic Reactions

• Genetic Factors

• Nutritional Imbalances

• Physical Agents

• Aging
Apoptosis

A. Apoptosis in Physiologic Situation

• The programmed destruction of cells during embryogenesis.

• Involution of hormone-dependent tissues upon hormone deprivation.

• Cell loss in proliferating cell populations

• Elimination of cells that have served their useful purpose

• Elimination of potentially harmful self-reactive lymphocytes.

• Cell death induced by cytotoxic T lymphocytes

B.Apoptosis in Pathologic Conditions:

• DNA damage : radiation, cytotoxic anticancer drugs, extremes

of temperature, and hypoxia can damage DNA, either directly
or through production of free radicals.

• Accumulation of misfolded proteins

• Cell injury in certain infections.

• Pathologic atrophy in organs after duct

parenchymal obstruction
Autophagy (“self-eating”) refers to lysosomal digestion of the cell's own
components. It is a survival mechanism in times of nutrient deprivation,
such that the starved cell subsists by eating its own contents and recycling
these contents to provide nutrients and energy.
Steps:
1.Intracellular organelles and portions of cytosol are first sequestered within
an autophagic vacuole.
2.The vacuole fuses with lysosomes to form an autophagolysosome,
in
which lysosomal enzymes digest the cellular components.
3.The starved cell eventually can no longer cope by devouring itself; at this
REFERENCES