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Cell Cycle

UPH FMS1 14-10-2009

Cell Cycle
Cells are generated from cells, the only
way to make more cells is by division of
those that already exist.
Cell must duplicate first its contents
and then divides in two. This cycle of
duplication and division known as the

cell cycle.

The Nobel Prize in Physiology

or Medicine 2001
for their discoveries of key regulators of the cell cycle

Leland H. Hartwell

Tim Hunt

Sir Paul M. Nurse

In the late 1960s Hartwell began using bakers

yeast to study how cells control their growth and
division. He identified more than 100 genes,
termed cell-division-cycle (CDC) genes, involved
in cell-cycle control. One such gene, named
cdc28, was demonstrated to control the first
phase and so became known as start.
Hartwell also found that the cycle includes
optional pauses, called checkpoints, that allow
time for repair of damaged DNA. His work
helped expand scientific understanding of
cancer and other diseases that occur when the
machinery of the cell cycle goes awry.

Mitosis and Cell Division Cycle

Cells that are growing and dividing
go through a repeating series of events
During the first phase (G1),
the cell grows and prepares
for DNA replication, occurs
in the subsequent S phase.
Further growth takes place
in the G2 phase, and finally
mitosis occurs in the M phase.

Mitosis and Meiosis

Mitosis is the process of cell division in
eukaryotes, in which the parental
chromosome number is conserved in each
of the daughter cells,
Meiosis is a two-cell-division process in
sexually reproducing eukaryotes that
results in cells (typically gametes) with onehalf the chromosome number of the original
parental cell.

The chromosomes duplicate once, through 2 successive divisions, 4 haploid cells
are produced, each with half the chromosome number of the parental cell

Meiosis involves two successive divisions of a diploid (2N)
eukaryotic cell of a sexually reproducing organism that
result in four haploid (N) progeny cells, each with half of
the genetic material of the original cell. Through the
mechanisms by which paternal and maternal
chromosomes segregate, and the process of crossingover, genetic variation is produced in the haploid cells.
Meiosis occurs only in sexually reproducing organisms.
Depending on the organism, it may produce haploid
gametes, which do not divide further but instead fuse to
produce a diploid zygote; or it may produce haploid spores,
which divide by mitotic cell cycles and produce unicellular
or multicellular organisms.

Mitosis is the process of nuclear division of either a diploid (2N) or haploid (N) eukaryotic
cell whereby two daughter nuclei are produced that are genetically identical to the parent
nucleus. Cell division usually follows nuclear division.

Mitosis usually results in the production of two progeny cells

that are genetically identical to the parent cell.

The Process of Mitosis

Various stages of Mitosis:


The Process of Mitosis

The critical steps in cell division include:

1. Ensuring the accurate doubling of a cell's
genetic information,
2. The genetic information is segregated
3. and separated into the two daughter cells.
This process must be carefully coordinated and
only initiated when the cell is ready. The
consequences of error in this process are
potentially devastating, either in terms of failed
division (and inability to grow) or division but with
genetic error (and the consequences of mutation).

the process of separating the new nuclei and half of the
parental cytoplasm into the new daughter cells

Cytokinesis is the division of cytoplasm in the
formation of daughter cells. The cell division that
follows telophase is called cytokinesis.
In plant cells, cytokinesis consists of the formation
of a new cell wall between the two daughter
In animal cell division, during or before the
completion of telophase, a contractile ring forms,
pinching apart two daughter cells, each
containing one nucleus.

Gene Segregation in Mitosis


Mitosis maintains a constant amount of genetic material from cell generation to cell generation. Consider a
hypothetical diploid cell with one chromosome. Consider also that this cell is Aa; that is, it is heterozygous for a
pair of alleles with A coming from one parent and a from the other parent.In the figure above, notice how we start
and end with cells having the same genotype.

The Nobel Prize in Physiology

or Medicine 2002
for their discoveries concerning genetic regulation of organ
development and programmed cell death

Sydney Brenner

H. Robert Horvitz

John E. Sulston

Press Release in 2001

The human body consists of hundreds of cell types, all originating
from the fertilized egg. During the embryonic and foetal periods, the
number of cells increase dramatically. The cells mature and become
specialized to form the various tissues and organs of the body. Large
numbers of cells are formed also in the adult body. In parallel with this
generation of new cells, cell death is a normal process, both in the
foetus and adult, to maintain the appropriate number of cells in the
tissues. This delicate, controlled elimination of cells is called
programmed cell death.
This year's Nobel Laureates in Physiology or Medicine have made
seminal discoveries concerning the genetic regulation of organ
development and programmed cell death. By establishing and using
the nematode Caenorhabditis elegans as an experimental model
system, possibilities were opened to follow cell division and
differentiation from the fertilized egg to the adult. The Laureates have
identified key genes regulating organ development and programmed
cell death and have shown that corresponding genes exist in higher
species, including man. The discoveries are important for medical
research and have shed new light on the pathogenesis of many

Apoptosis is the term given when programmed cell death
(PCD) occurs in multicellular organisms.

APOPTOSIS is one of the main types of programmed cell death

which involves a series of biochemical events leading to specific
cell morphology characteristics and ultimately death of cells.
Characteristic cell morphology of cells undergoing apoptosis
include blebbing, changes to the cell membrane such as loss of
membrane asymmetry and attachment, cell shrinkage, nuclear
fragmentation, chromatin condensation, and chromosomal DNA
fragmentation. Apoptosis differentiates from necrosis as the
processes associated with apoptosis in disposal of cellular
debris do not damage the organism in apoptosis.
NECROSIS is a form of traumatic cell death that results from
acute cellular injury. Apoptosis in contrast to necrosis, confers
advantages during an organism's life cycle.

Development of an organ or tissue is often preceded by the
extensive division and differentiation of a particular cell, the
resultant mass is then "pruned" into the correct form by
apoptosis, which results in cell shrinkage and fragmentation.
Such shrinkage and fragmentation allow the cells to be
phagocytosed and their components reused without releasing
potentially harmful intracellular substances such as hydrolytic
enzymes into the surrounding tissue.
During development, apoptosis is tightly regulated and
different tissues use different signals for inducing apoptosis. In
birds, bone morphogenetic proteins (BMP) signaling is used to
induce apoptosis in the interdigital tissue. In Drosophila flies,
steroid hormones regulate cell death. Developmental cues
can also induce apoptosis, such as the sex-specific cell death
of hermaphrodite specific neurons in C. elegans males
through low TRA-1 transcription factor activity (TRA-1 helps
prevent cell death).

Between 50 billion and 70 billion cells
die each day due to apoptosis in the
average human adult. For an average
child between the ages of 8 and 14,
approximately 20 billion to 30 billion
cells die a day. In a year, this amounts
to the proliferation and subsequent
destruction of a mass of cells equal to
an individual's body weight.

Defective apoptotic processes

have been implicated in an
extensive variety of diseases.
Excessive apoptosis causes
hypotrophy, such as in ischemic
damage, whereas an insufficient
amount results in uncontrolled cell
proliferation, such as cancer

Apoptosis occurs when a cell is damaged beyond repair,
infected with a virus, or undergoing stressful conditions such
as starvation. Damage to DNA from ionizing radiation or
toxic chemicals can also induce apoptosis via the actions of
the tumor-suppressing gene p53. The "decision" for
apoptosis can come from the cell itself, from the surrounding
tissue, or from a cell that is part of the immune system. In
these cases apoptosis functions to remove the damaged
cell, preventing it from sapping further nutrients from the
organism, or halting further spread of viral infection.
Apoptosis also plays a role in preventing cancer. If a cell is
unable to undergo apoptosis because of mutation or
biochemical inhibition, it continues to divide and develop into
a tumor. For example, infection by papillomaviruses causes
a viral gene to interfere with the cell's p53 protein, an
important member of the apoptotic pathway. This
interference in the apoptotic capability of the cell plays a role
in the development of cervical cancer

or Homeodynamics
In the adult organism, the number of cells is
kept relatively constant through cell death
and division. Cells must be replaced when
they malfunction or become diseased, but
proliferation must be offset by cell death.
This control mechanism is part of the
homeostasis required by living organisms to
maintain their internal states within certain
limits. Some scientists have suggested
homeodynamics as a more accurate term.

Homeostasis is achieved when

mitosis rate = cell death rate
If this equilibrium is disturbed, one of two
potentially fatal disorders occurs:
1. the cells divide faster than they die, resulting in
the development of a tumor.
2. the cells divide slower than they die, causing
cell loss.

Apoptosis Signals
The process of apoptosis is controlled by a diverse
range of cell signals, which may originate either
extracellularly (extrinsic inducers) or intracellularly
(intrinsic inducers). Extracellular signals may
include toxins, hormones, growth factors, nitric
oxide or cytokines, and therefore must either cross
the plasma membrane or transduce to effect a
response. These signals may positively or
negatively affect apoptosis.
Binding and subsequent initiation of apoptosis by a
molecule is termed positive induction, whereas
the active repression or inhibition of apoptosis by a
molecule is termed negative induction

Intracellular Apoptotic Signalling

A cell initiates intracellular apoptotic signalling in
response to a stress, which may bring about cell
suicide. The binding of nuclear receptors by
glucocorticoids, heat, radiation, nutrient
deprivation, viral infection, hypoxia and
increased intracellular calcium concentration, for
example, by damage to the membrane, can all
trigger the release of intracellular apoptotic
signals by a damaged cell. A number of cellular
components, such as poly ADP ribose
polymerase, may also help regulate apoptosis

Apoptotic Pathway
Before the actual process of cell death is
precipitated by enzymes, apoptotic signals
must cause regulatory proteins to initiate the
apoptosis pathway. This step allows apoptotic
signals to cause cell death, or the process to
be stopped, should the cell no longer need to
die. Several proteins are involved, but two main
methods of regulation have been identified:
targeting mitochondria functionality, or
directly transducing the signal via adaptor
proteins to the apoptotic mechanisms.

Mitochondrial regulation
The mitochondria are essential to multicellular life.
Without them, a cell ceases to respire aerobically
and quickly dies, a fact exploited by some
apoptotic pathways. Apoptotic proteins that target
mitochondria affect them in different ways. They
may cause mitochondrial swelling through the
formation of membrane pores, or they may
increase the permeability of the mitochondrial
membrane and cause apoptotic effectors to leak
out. There is also a growing body of evidence that
indicates that nitric oxide is able to induce
apoptosis by helping to dissipate the membrane
potential of mitochondria and therefore make it
more permeable.