2. Why Would a Cell Divide?
• As cells absorb nutrients and get larger, the volume
of the cell increases faster than the surface area
• This means that a cell can no longer absorb nutrients
and get rid of wastes fast enough to support its demands
(volume and size restrictions)
• So what’s a cell to do? ……………. DIVIDE !!!!
2
3. Why Would a Cell Divide?
Besides growth a cell would also divide in case of:
– Repair or Replacement
– Cancer
Different cells divide at different rates:
Most mammalian cells = 12-24 hours
Some bacterial cells = 20-30 minutes
3
4. Getting Older…
• All cells are only allowed to complete a certain number
of divisions
• Then they die (programmed cell death)
How does cell division pattern change over a lifetime?
• Childhood = cell division > cell death
• Adulthood = cell division = cell death
• The Later Years = cell division < cell death
4
5. Cell Cycle Tidbits
How long is one cell cycle?
• Depends on the cell
• skin cells = ~24 hours
• nerve cells = never after maturity
• cancer cells = very short
• Remember: every cell only has a certain # of divisions
it can undergo, then it dies = apoptosis (programmed cell
death)
5
6. In summary any time new cells are
required, mitosis is required:
Embryonic development: A fertilized egg (zygote) will undergo mitosis
and differentiation in order to develop into an
embryo
Growth: Multicellular organisms increase their size by increasing their
number of cells through mitosis
Asexual reproduction: Certain eukaryotic organisms may reproduce
asexually by mitosis (e.g. vegetative reproduction)
Tissue Repair: Damaged tissue can recover by replacing dead or damaged
cells
6
7. CELL REPRODUCTION
• Cell Division: Process by which a cell divides to form
two new cells (daughter cells)
• Three types of cell division, or cell reproduction
– Prokaryotes (bacteria)
• Binary fission divides forming two new identical cells
– Eukaryotes
• Mitosis
– Cell or organism growth
– Replacement or repair of damaged cells
• Meiosis
– formation of sex cells, or gametes 7
8. Why do cells divide?
1. DNA Overload
– If cells grow without limit, an “information crisis” would
develop
– DNA cannot serve the needs of the increasing size of cell
2. Exchange of Materials
– Food and oxygen have to cross membrane very quickly
– Waste must get out
– If cell is too large, this occurs too slowly and cell will die
8
9. PROKARYOTIC CELL DIVISION
• Binary fission
– 3 main steps:
1. DNA Replication – DNA is copied,
resulting in 2 identical chromosomes
2. Chromosome Segregation – 2 chromosomes separate, move
towards ends (poles) of cell
3. Cytokinesis – cytoplasm divides, forming 2 cells
– Each new daughter cell is genetically identical to parent cell
9
11. CELL CYCLE-INTERPHASE
• Interphase: Period of growth and DNA replication
between cell divisions
Three phases:
– G1 Phase
• Cell increases in size
– S Phase
• Replication of chromosomes
– Now two strands called sister chromatids
joined by a centromere
– G2 Phase
• Organelles double
• New cytoplasm forms
• All other structures needed for mitosis form
11
12. 12
• Centromere - primary constriction of a chromosome
• Kinetochores - two discs of proteins, located at the centromere, on opposite
sides of the chromosome.
Note: The microtubules that attach to the chromosomes actually attach to the
kinetochores (which is why those microtubules are called kinetochore
microtubules).
13. • DNA containing cell’s genetic code
• Each chromosome has a matching pair
-- Homologous Pair
• During interphase,
–each chromosome copies itself
13
14. EUKARYOTIC CELL DIVISION
• DNA found on chromosomes located in nucleus of cell
• Cell cycle continuous process
– Cells grow
– DNA replicated
– Organelles duplicated
– Divide to form daughter cells
– 2 Main Steps :
1: Mitosis (4 steps: Prophase, Metaphase, Anaphase, Telophase) -
Nucleus divides
2: Cytokinesis – Cytoplasm divides, forming 2 cells
Each new daughter cell is genetically identical to parent cell
14
15. • Mitosis = nuclear division
• Mitosis is followed by cytokinesis (cell division)
• The steps of mitosis ensure that each new cell has
the exact same number of chromosomes as the
original
15
Pericentriolar Matrix (PCM):
Amorphous mass of protein which makes
up the part of the animal centrosome that
surrounds the two centrioles
17. MITOSIS
• Process that divides cell nucleus to produce two new
nuclei each with a complete set of chromosomes
• Continuous process
• Four phases (PMAT)
– Prophase
– Metaphase
– Anaphase
– Telophase
17
23. Occurs at end of Mitosis
– Division of the cytoplasm to form 2 new daughter
cells
– Organelles are divided
– Daughter cells are genetically identical
Cells return to interphase
23
24. Cytokinesis occurs after mitosis and is different in plant and animal cells.
Animal cells Plant cells
• A ring of contractile protein (microfilaments)
immediately inside the plasma membrane at
the equator pulls the plasma membrane
inward.
• The inward pull on the plasma membrane
produces the characteristic cleavage furrow.
• When the cleavage furrow reaches the centre
of the cells it is pinched apart to form two
daughter cells.
• During telophase, membrane-enclosed vesicles derived
from the Golgi apparatus migrate to the centre of the
cell.
• Vesicles fuse to form tubular structures.
• The tubular structures merge (with the addition of more
vesicles) to form two layers of plasma membrane (i.e.
the cell plate)
• The cell plate continues to develop until it connects
with the existing cell’s plasma membrane.
• This completes the division of the cytoplasm and the
formation of two daughter cells.
• Vesicles deposit, by exocytosis, pectins and other
substances in the lumen between the daughter cells to
form the middle lamella (‘gluing’ the cells together)
• Both daughter cell secrete cellulose to form their new
adjoining cell walls. 24
26. Control of the Cell Cycle
• Regulatory proteins called cyclins control the
cell cycle at checkpoints:
– G1 Checkpoint decides whether or not cell will divide
– S Checkpoint determines if DNA has been properly
replicated
– Mitotic Spindle Checkpoint ensures chromosomes
are aligned at mitotic plate
26
• Cyclin is a family of proteins that control the progression
of cells through the cell cycle by activating cyclin-
dependent kinase (Cdk) enzymes
28. CYCLINS ARE INVOLVED IN THE CONTROL OF THE CELL CYCLE
http://upload.wikimedia.org/wikipedia/commons/thumb/9/99/Protein_CCNE1_PDB_1w98.png/800px-Protein_CCNE1_PDB_1w98.png
Triggers cells to move
from G0 to G1 and from
G1 into S phase.
prepares the cell for
DNA replication in S
phase.
activates DNA
replication inside the
nucleus in S phase.
promotes the assembly
of the mitotic spindle
and other tasks in the
cytoplasm to prepare
for mitosis.
Progression through parts of the cell cycle are affected
in various ways by specific cyclins
28
Figure: Expression of human cyclins through the cell cycle
29. TWO KEY COMPONENTS OF THE CELL-CYCLE
CONTROL SYSTEM
• G1/S-cyclins bind Cdks at the end of G1 and
commit the cell to DNA replication.
• S-cyclins bind Cdks during S phase and are
required for the initiation of DNA replication.
• M-cyclins promote the events of mitosis.
• G1-cyclin helps promote passage through Start
or the restriction point in late G1.
29
• Cell Cycle Control System: Set of switches that act as checkpoints
between each step of the cell cycle
• Checkpoint Switches: Switch on/off proteins for DNA replication (by
kinase protein) or dephosphorylation (done by phosphatases)
• Cyclins: Set of proteins that controls Checkpoint switches
30. CORE OF THE CELL-CYCLE CONTROL SYSTEM
30
• Anaphase Promoting Complex
(APC): It is a Ubiquitin Ligase.
Activated once M-Cdk begins to from.
It adds Ubiquitin to the cyclin (helps
rapid degradation of M-Cdk once the
cell enters Mitosis).
31. AN OVERVIEW OF THE CELL-CYCLE CONTROL SYSTEM
31
An overview of the cell cycle control system: The core is consists of a series of
Cyclins-Cdk complexes (yellow). The activity of each complex is influenced by various
inhibitory checkpoint mehanisms which provide information about the extracellular
environment, cell damage and incomplete cell cycle events.
P53: It is a 53 kiloDalton protein (Tumor Suppressor Protein). 1) Activates DNA
repair proteins if DNA has sustained damage, 2) Can initiate apoptosis if DNA damage
prove to be irreparable, 3) Arrest growth by holding the cell cycle at G1/S phase
regulation point on DNA damage recognition
Cdc25: (Cdc name derived from Cell division cycle). It is a dual-specificity phospahatase
(a subclass of protein tyrosine phospahatase). Cdc25 removes inhibitory phospahate
residue from target Cdks
• Proteolysis of
mitotic cyclins
depends on APC.
• Proteolysis APC
requires
interaction with
Hct1.
• Phosphorylation of
Hct1 by CDKs
blocked the Hct1-
APC interaction
32. Cdk / G1
cyclin
Cdk / G2
cyclin (MPF)
G2
S
G1
C
M
G2 / M checkpoint
G1 / S checkpoint
APC
Active
Inactive
Active
Inactive
Inactive
Active
mitosis
cytokinesis
MPF = Mitosis Promoting Factor
APC = Anaphase Promoting Complex
• Replication completed
• DNA integrity
Chromosomes attached at
metaphase plate
Spindle checkpoint
• Growth factors
• Nutritional state of cell
• Size of cell
32