dr. Risma Ikawaty, Ph.D.

13 September 2019
 The cell cycle
• The complex sequence of events by which
cells grow and divide.

• In eukaryotic cells, the phases of the cell cycle

include Mitotic phase and Interphase

The dividing cell spends most of 1. Gap 1 phase (G 1)

its time in interphase as it grows 2. Synthesis phase (S)
in preparation for cell division. 3. Gap 2 phase (G2)
 Mitosis phase
Involves:
1. Separation of nuclear chromosomes
2. Cytokinesis (division of cytoplasm forming
two distinct cells)

At the end of the mitotic cell cycle, two

distinct daughter cells are produced.
Each cell contains identical genetic material.
 Time to complete one cell cycle
• Varies depending on the type of cell.
• Divide rapidly and constantly  blood cells in
bone marrow, skin cells, and cells lining the
stomach and intestines.
• Divide when needed to replaced damaged or
dead cells  cells in kidney, liver, and lungs.
• Stop dividing once mature  nerve cells
• The cell cycle also occurs in the replication of
sex cells, or meiosis. Upon completion of
the cell cycle in meiosis, four daughter
cells are produced.
 Interphase
• During this segment of the cell cycle, a cell doubles its
cytoplasm and synthesizes DNA.
• It is estimated that a dividing cell spends about 90-95%
of its time in this phase.

• G1 phase:
The period prior to the synthesis of DNA.
The cell increases in mass and organelle number in
preparation for cell division.
Animal cells in this phase are diploid two sets of
chromosomes.
 Interphase
• S phase:
DNA is synthesized. In most cells, there is a narrow
window of time during which DNA replication occurs.
The chromosome content is doubled in this phase.

• G2 phase:
The period after DNA synthesis has occurred but prior to
the start of mitosis.
The cell synthesizes additional proteins and continues to
increase in size.

In the latter part of interphase, the cell still has nucleoli

present.
Stages of Mitosis
• Prophase  Prepare
• Metaphase  Middle
• Anaphase  Away/Apart
• Telophase  Two
• Prophase: In this stage, changes occur in both the
cytoplasm and nucleus of the dividing cell. The
chromatin condenses into discrete chromosomes. The
chromosomes begin to migrate toward the cell center.
The nuclear envelope breaks down and spindle fibers
form at opposite poles of the cell.
During prophase, a number of important
changes occur:
• Chromatin fibers become coiled into
chromosomes, with each chromosome having
two chromatids joined at a centromere.
 Prophase
• Prophase is the first true
step of the mitotic process.
• The mitotic spindle,
composed of microtubules
and proteins, forms in the
cytoplasm.
• The two pairs of centrioles
(formed from the
replication of one pair in
Interphase) move away
from one another toward
opposite ends of the cell
due to the lengthening of
the microtubules that form
between them.
• Polar fibers, which are microtubules that make
up the spindle fibers, reach from each cell
pole to the cell's equator.
• Kinetochores, which are specialized regions in
the centromeres of chromosomes, attach to a
type of microtubule called kinetochore fibers.
• The kinetochore fibers "interact" with the
spindle polar fibers connecting the
kinetochores to the polar fibers.
• The chromosomes begin to migrate toward
the cell center.
• Metaphase: In this stage, the nuclear
membrane disappears completely. The spindle
fully develops and the chromosomes align at
the metaphase plate (a plane that is equally
distant from the two poles).
Metaphase

• The spindle reaches maturity and the chromosomes align at the

metaphase plate (equally distant from the two spindle poles).
During this phase, a number of changes occur:
• The nuclear membrane disappears completely.
• Polar fibers (microtubules that make up the spindle fibers) continue
to extend from the poles to the center of the cell.
• Chromosomes move randomly until they attach (at their
kinetochores) to polar fibers from both sides of their centromeres.
• Chromosomes align at the metaphase plate at right angles to the
spindle poles.
• Chromosomes are held at the metaphase plate by the equal forces
of the polar fibers pushing on the centromeres of the
chromosomes.
• Anaphase: In this stage, paired chromosomes
(sister chromatids) separate and begin moving
to opposite ends (poles) of the cell. Spindle
fibers not connected to chromatids lengthen
and elongate the cell.
Anaphase

During anaphase, the following key changes occur:

• The paired centromeres in each distinct chromosome begin to
move apart.
• Once the paired sister chromatids separate from one another, each
is considered a "full" chromosome. They are referred to as daughter
chromosomes.
• Through the spindle apparatus, the daughter chromosomes move
to the poles at opposite ends of the cell.
• The daughter chromosomes migrate centromere first and the
kinetochore fibers become shorter as the chromosomes near a
pole.
• In preparation for telophase, the two cell poles also move further
apart during the course of anaphase. At the end of anaphase, each
pole contains a complete compilation of chromosomes.
• Telophase:
The chromosomes are cordoned off into distinct new
nuclei.
The genetic content of the cell is divided equally into
two parts.
Cytokinesis begins prior to the end of mitosis and
completes shortly after telophase.
Telophase
The following changes occur:
• The polar fibers continue to lengthen.
• Nuclei begin to form at opposite poles.
• The nuclear envelopes of these nuclei form from
remnant pieces of the parent cell's nuclear envelope
and from pieces of the endomembrane system.
• Nucleoli also reappear.
• Chromatin fibers of chromosomes uncoil.
• After these changes, telophase/mitosis is largely
complete. The genetic contents of one cell have been
divided equally into two.
Cytokinesis

• Cytokinesis is the division of the cell's

cytoplasm.
• It begins prior to the end of mitosis in
anaphase and completes shortly after
telophase/mitosis.
• At the end of cytokinesis, two genetically
identical daughter cells are produced. These
are diploid cells, with each cell containing a
full complement of chromosomes.
• Once a cell has completed the cell cycle, it
goes back into the G 1 phase and repeats the
cycle again.

• Cells in the body can also be placed in a non-

dividing state called the Gap 0 phase (G 0) at
any point in their life. Cells may remain in this
stage for very long periods of time until they
are signaled to progress through the cell cycle
as initiated by the presence of certain growth
factors or other signals.
• Cells that contain genetic mutations are
permanently placed in the G 0 phase to ensure
that they are not replicated.

• When the cell cycle goes wrong, normal cell

growth is lost. Cancer cells may develop,
which gain control of their own growth signals
and continue to multiply unchecked.
 MITOSIS VS MEIOSIS
• In meiosis, four daughter cells are produced.
These cells are haploid cells, containing one-
half the number of chromosomes as the
original cell. Sex cells undergo meiosis. When
sex cells unite during fertilization, these
haploid cells become a diploid cell.
 The Cell Cycle Control System
Is like a clock, regulated by both internal and external controls, and has specific
checkpoints where the cell cycle stops until a go-ahead signal is received

Cell Cycle Clock

Specific time to control:
- Correct order (once per cycle)
- Binary switch on/off system
- Adaptability: specific cell types or environment

Cell Cycle Checkpoint

Delay the cell cycle progression or arrest the cell
cycle in response to signals  provide time for
DNA repair or prevent “the disaster”
 Cell Cycle Clock
• Capacity of cell to grow and divide is control is
controlled by a set of proteins which integrate
the inhibitory and stimulatory signals
regulated by or produced within the cell.
 Major Cell Cycle Regulatory
Proteins
• Proteins:
1. Cyclin-dependent kinases (Cdk) first
discovered in yeast
2. Different kinds of cyclins; levels oscillate at
different stages of cycle
Cyclins and Cdk constitute the core
components of the cell cycle clock
 Cyclin dependent kinase (Cdk)

• A cell division control protein

• Active only when bound to cyclin
- G1-phase  cdk 4,6
- Late G1/ S-phase  Cdk 2
- M-phase  Cdk1
 Cyclins
- A protein whose amount varies cyclically;
- When in high concentrations binds to cdk
makes MPF.
1. G1-phase cyclins (D cyclins)
2. S-phase cyclins (cyclins E and A)
• Cdk must be phosphorylated
• Cyclin and Cdk must be bound together to be
active
• Initial cyclin-Cdk complex is inactive
• A series of phosphorylation and dephos-
phorylation steps  Active Complex is called
MPF (mitosis-promoting factor)
 MPF (mitosis-promoting factor)
• Complex of two proteins cdk + cyclin
• MPF is a kinase enzyme, one that switches
on/off target cell cycle proteins by
phosphorylating them
• PPT LECTURES\METPEN\MICROBIOLOGY\mitosis 3d
animation Phases of mitosiscell division.mp4

• PPT LECTURES\METPEN\MICROBIOLOGY\Mitosis Rap Mr. Ws

Cell Division Song.mp4