Transcript The Cell Cycle - Bio-Guru

The Cell Cycle
Chapter 12
& part of chapter 11
All cells come from pre-existing cells
Sperm that did not make it in
• One characteristic that
distinguishes living from
non-living is the ability to
reproduce
• Cellular reproduction
allows the continuity of
life, growth and repair
• Cellular reproduction can
be asexual or vegetative,
or sexual
8-cell human embryo
Asexual / Vegetative Reproduction
• Does not involve exchange of genetic material
• Daughter cell is a clone of parent cell (genetically
identical)
• Performed by:
- bacteria (binary fission),
- protists
- yeast (budding)
- certain plants (sprouting of potato eyes)
Asexual / Vegetative Reproduction
Plant cuttings will sprout roots, as will a potato, which is a
tuber – a modified, underground stem.
Asexual Reproduction – Binary Fission
The prokaryotic chromosome is bound to
plasma membrane, in the nucleoid region
of the cell. It remains bound, even after it
is duplicated, as the cell begins to
elongate. This causes the parent and
daughter chromosomes to separate –
eventually the cell splits into two identical
cells (Clones)
Asexual reproduction - budding
Mold
Yeast
Hydra
Genetically
identical
clones
Asexual is good – sexual is better!
• Although asexual reproduction is energy and
time efficient, sexual reproduction allows genetic
variations that may increase the species
chances of survival
• Most organisms that normally reproduce
asexually, can also reproduce sexually, i.e they
can create offspring that are genetically different
(not clones)
• Sexual reproduction for these organisms usually
follows environmental stress such as a lack of
food and other resources
Asexual reproduction in eukaryotes is known
as MITOSIS
• Mitosis is the division
of the nucleus and its
contents
• Mitosis is followed by
cytokinesis – the
division of the
cytoplasm
All somatic cells reproduce mitotically
• Somatic cells are all the cells of the body,
except the gametes (egg and sperm)
• Skin cells, liver cells, cells that line the G.I.
tract, etc. are constantly dividing, to
replace dead cells
• Other cells such as neurons, adipose
cells, muscle cells, etc. never or rarely
divide
The Cell Cycle
• A typical human cell undergoes a division about every
24 hours (there are many exceptions!)
• The cell cycle is basically an alternation of 2 major
phases – Mitosis and Interphase
• Interphase is the phase in which the cell spends 23 of
the 24 hours – the cell grows, carries out its
“housekeeping duties” and its specialized activities
• Mitosis takes about 1 hour
The Cell Cycle, cont’d.
Interphase can be broken down into 3 distinct subphases:
– G1 (Known as gap 1)
– S (for synthesis of DNA)
– G2 (gap 2)
Cells that do not divide are considered to be in a
phase called G0 – where they carry on normal
housekeeping and do not prepare to divide
The Cell Cycle
Phases of Interphase
• G1 phase: The period prior to the synthesis of DNA.
In this phase, the cell prepares for cell division
- proteins are synthesized
- the cell increases in mass
• S phase: The period after G1, where all genetic
material (DNA) is synthesized
• G2 phase: The period after DNA synthesis has
occurred but prior to the start of mitosis.
- cell continues to increase in size
- centrosome divides into 2
- In animal cells, each centrosome has 2 centrioles
How DNA Packs into a Metaphase Chromosome
Chromosomes
A human Karyotype
All somatic cells are Diploid (2n)
• The cells have 2 versions of every DNA strand or chromosome
• The 2 versions are called homologous chromosomes
•One homologue comes
from the sperm and the
other from the egg
•Human somatic cells
have 46 chromosomes –
or 23 homologous
chromosome pairs
DNA (chromosome) replication
• The cell has to replicate
(duplicate) all its DNA
• The duplicated DNA is then
organized into distinct bundles
called chromosomes – the
duplicates are connected to each
other at the centromere
• Each duplicated DNA strand is
called a sister chromatid
• Human cells still have 46
chromosomes, and 23
homologous pairs, but 92 sister
chromatids
DNA Replication
(p-arm)
(q-arm)
Duplicated
Chromosome
What is the centromere?
• A centromere is a region of DNA typically found
near the middle of a chromosome where two
sister chromatids come in contact.
• The DNA in the centromere region typically
contains tandem repetitive sequences, often
called "satellite DNA" - it is considered “junk”
DNA – as it doesn’t code for RNA
• During mitotic division, a transient structure
called kinetochore is formed on top of the
centromeres. The kinetochores are the sites
where the spindle fibers attach.
The duplicated chromosome
The mitotic spindle at Metaphase
(Animal Cells only)
(Animal Cells only)
Centriole and centrosome
duplication
•Centrioles exist in pairs, in the centrosome region
of animal cells
•Centrioles have microtubules arranged in 9 triplets
Centrosomes and Centrioles
• The centrosome is the microtubule-organizing center (MTOC) of animal
cells. It contains a pair of centrioles.
• During interphase of an animal cell, the centrioles and in the centrosome
are duplicated (not clear how ).
• At first the replicated pairs of centrioles remain in the same centrosomes
region. Eventually, in Prophase, the original centrosome divides in two.
• Now each new centrosome has a pair of centrioles.
• These new centers synthesize microtubules in star-shaped clusters
known as asters.
• As the asters move to opposite poles of the cells, the microtubules, with
the help of the centrioles, become organized into a spindle-shaped
formation that spans the cell.
• These spindle fibers act as guides for the alignment of the chromosomes
as they separate later during the process of cell division.
Centrioles/centrosome – Important or not?
• Though centrioles and the centrosome play a role in the mitosis of
animal cells, plant and fungal cells are able to reproduce without
them – they have some other MTOC organelles.
• Researchers have, therefore, been very interested in determining
exactly how important the organelles really are.
• Studies have shown that certain animal cells, particularly female
gametes (oocytes), can successfully divide even when their
centrioles are destroyed.
• Some investigators have also found, however, that the absence of
centrioles in animal cells is associated with an increased number of
divisional errors and substantial delays in the mitotic process,
especially before chromosome segregation.
• Consequently, it has been suggested that centrioles evolved as a
refinement of the cell, making mitosis a much more efficient and less
error-prone process.
Phases of Mitosis
•
•
•
•
•
Prophase
Prometaphase
Metaphase
Anaphase
Telophase (followed immediately by
cytokinesis)
Phases of Mitosis
G2 of Interphase
Prophase
Anaphase
Prometaphase
Telophase & beginning
of cytokinesis
Metaphase
Completion of cytokinesis
Prophase
1. Nuclear chromatin starts to become
organized and condenses into thick
strands that eventually become
chromosomes observable in the
optical microscope.
2. The nucleoli, primarily responsible
for the production of ribosomal
RNA, begin to disappear as the
chromosomes condense.
3. The mitotic spindle, which is
assembled by the centrosomes
begins to appear along the
periphery of the nuclear membrane.
These are called asters or stars
4. Centrosomes begin to move apart
Prometaphase
• Nuclear membrane begins to
fragment
• This allows spindle fibers to invade
the nuclear space and interact with
chromosomes
• Chromosomes are extremely
dense and each sister chromatid
has a protein complex at the
centromere called a kinetochore
• Some microtubules (spindle fibers)
attach to chromosome
kinetochores
• Other microtubules (spindle fibers)
interact with those from the
opposite pole of the mitotic spindle
Metaphase
• Centrosomes are at opposite
poles
• The chromosomes, attached
to the kinetochore
microtubules, begin to align
in a single plane (known as
the metaphase plate)
midway between the spindle
poles
• Each sister chromatid’s
kinetochore is attached to a
spindle fiber coming from
opposite poles
Anaphase
• Sister chromatids pull apart
and are now considered
daughter chromosomes
• * Hypothesis - the motor
proteins in the kinetochore
move the chromosome along
the microtubule toward the
poles.
• Nonkinetochore
microtubules lengthen,
pushing the centrosomes
further apart.
• At the end of anaphase, each
group of chromosomes is
clustered at opposite poles.
Telophase
• In animal cells, the cleavage
furrow begins to form due to
an actin ring (microfilaments)
• In plant cells there is no
cleavage furrow – a cell plate
forms (discussed later)
• Nuclear membrane begins to
re-form
• The mitotic spindle begins to
disassemble
• Chromosomes begin to return
to chromatin state
• Nucleolus begins to reappear
Interphase
• Nucleus contains
chromatin
• Only one set of centrioles
(one centrosome)
• Fully formed nuclear
membrane
• Fully formed nucleolus
Centrioles will replicate
once the cell is ready to
divide again
What happens in the
Kinetochore during
Anaphase?
1. Motor proteins called Dyenins “walk”
along the microtubules, carrying the
chromosomes toward the spindle
poles.
2. The microtubules get disassembled
as the chromosome moves toward
the poles.
G2 - Interphase
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis
PROPHASE
PROMETAPHASE
METAPHASE
ANAPHASE
TELOPHASE
Cytokinesis in Animal Cells
Cleavage Furrow
Contractile ring made of actin microfilaments, “pinches” the cell into two.
Cytokinesis in Plant Cells
Plant cells cannot be “pinched” into
two new daughter cells, because
of the cell wall.
The Golgi body secretes cell wall
material packaged in transport
vesicles that line up on the
equator. These vesicles fuse to
create a cell plate.
The cell plate divides the cell in
two. The cell plate becomes the
cell wall.
Cyclical changes in DNA of cell
Cell Cycle Checkpoints
• If cell size inadequate
– G1 or G2 arrest
• If nutrient supply inadequate
– G1 arrest
• If an essential external stimulus is
lacking
– G1 arrest (at R)
• If the DNA is not replicated
– S arrest
• If DNA damage is detected
– G1 or G2 arrest
• If the spindle formation is improper,
chromosome misalignment
– M-phase arrest
R
Cdks and cyclins
Cyclin-dependent kinases (Cdks) are enzymes that are present in the cell cytoplasm at all
times.
However, they are inactive unless they are bound by a specific partner-protein called a
cyclin to form a Cdk-cyclin complex
The amount of cyclins in the cell changes – because they get degraded
A Cdk-cyclin complex will push the cell cycle forward.
Types of Cyclins and Cdks
• There are many types of cyclins, but the 4 main ones
are:
–
–
–
–
Cyclin D (G1 cyclin)
Cyclin E (S-phase cyclin)
Cyclin A (S-phase and mitotic cyclin)
Cyclin B (mitotic cyclin)
• These are the 3 main cdks
– Cdk4 (G1 Cdk)
– Cdk2 (S-phase Cdk)
– Cdk1 (mitotic Cdk)
• The complex of Cdk1 and cyclin B is called mitosis
promoting factor (MPF) a.k.a maturation promoting
factor
Cyclin Concentration
Rise and fall of cyclins
Mitosis
MPF (Mitosis Promotion Factor)
Cyclins are degraded by proteosomes, after they are tagged for
degradation with a protein called ubiquitin. Ubiquitin is a big “TRASH”
sign and proteasomes are protein shredders.
Protein ubiquitination and degradation
What is Cancer?
Uncontrolled Cell division
Loss of cell cycle control and checkpoints
What does a cancerous cell look like?
•Large or multiple nuclei
•Irregular shape
•Cells overlapping neighboring cells – loss of density-dependent or contact
inhibition
Tumors
•
Benign - A spontaneous
growth of tissue which forms
an abnormal mass is called a
tumor. A tumor that is
noninvasive and
noncancerous is referred to
as a benign tumor.
•
Malignant - A tumor that
invades neighboring cells
and is cancerous is referred
to as a malignant tumor.
•
Matastasis – Cancer that has
spread to other tissues.
How we naturally fight cancer cells
• Tumor suppressor genes like p53
– Can arrest the cell cycle
– Can launch the apoptotic pathway, causing
the rogue cells to lyse
A mutation in the p53 gene can lead to cancer
• Immune cells (WBCs) such as NK cells
can attack and lyse tumor cells
– Some immune cells can signal the rogue cells
to launch the apoptotic pathways
Apoptosis vs. Necrosis
• Necrosis is traumatic cell death caused by
injury. Necrosis of cells will lyse and
damage neighboring cells by spilling all
the intracellular contents. This causes
inflammation of neighboring tissues and
further trauma.
Apoptosis vs. Necrosis
• Apoptosis is programmed cell death, which prevents
damage to neighboring cells by controlling how the
affected cell dies
• During apoptosis, the cell's cytoskeleton is broken down,
causing multiple bulges in the membrane. This is called
blebbing.
• These blebs (a.k.a. apoptotic bodies) can separate from
the cell, taking a portion of cytoplasm with them.
Phagocytic cells eventually consume these fragments.
• Hence, apoptosis keeps damaged cellular contents from
spilling out and damaging other cells.
Blebbing in Apoptosis
Necrotic cells
Necrotic cell with multiple lesions
Apoptotic cell with blebbing
Signal Transduction Pathways
• What are they?
– Signal transduction refers to any process by which a
cell converts one kind of signal or stimulus into
another.
– A large number of proteins, enzymes and other
molecules participate in a "signal cascade“
• What is the end result?
– Either the activation or inhibition of a certain enzyme
in the cytoplasm
– Either the expression or suppression of a particular
gene
Just a few examples of Signal
Transduction Pathways
• Cell Division signals
• Apoptotic signals
• Insulin pathways
Apoptotic
Pathways
Insulin Signaling Pathway
The binding of insulin to its receptor on a cell starts a cascade of
cellular events which finally leads to the uptake of glucose and
the lowering of blood glucose levels.
THE END