Cyto EXONotes 3 The Cell Cycle FIXED
Cyto EXONotes 3 The Cell Cycle FIXED
Cyto EXONotes 3 The Cell Cycle FIXED
CYCLE
JOMARI B. CADDAUAN, RMT
credits: rbmrmt
CELL CYCLE
→sequence of activities as a cell prepares for division
and then divides
2 major stages:
1. INTERPHASE (not dividing)
2. MPHASE (dividing)
MEOSIS
→half the amount of genetic material in
somatic cells, or 23 single chromosomes =SEX CELLS OR GERM CELLS
Functions:
▪ REPRODUCTION → prokaryotic cell = BINARY FISSION
▪ RENEWAL OR → normal wear and tear or accidents
REPAIR
Postsynthesis gap M
(4 hours)
Synthesis
of DNA
(9 hours)
INTERPHASE
It is the extended period of growth and development
between cell divisions.
❑ Although little activity can be observed with a light
microscope, the cell is quite busy: DNA is being
synthesized, RNA and proteins are being produced, and
hundreds of biochemical reactions necessary for cellular
functions are taking place.
❑ In addition to growth and development, interphase
includes several CHECKPOINTS, which regulate the cell cycle
by allowing or prohibiting the cell’s division.
❑ These checkpoints, like the checkpoints in the M phase,
ensure that all cellular components are present and in
good working order before the cell proceeds to the next
stage.
❑ Checkpoints are necessary to prevent cells with
damaged or missing chromosomes from proliferating.
❑ Defects in checkpoints can lead to unregulated cell
growth, as is seen in some cancers.
❑ By convention, interphase is divided into three
subphases: G1, S, and G2.
G1
❑ Interphase begins with G1 (for gap 1).
❑ In G1, the CELL GROWS , and proteins necessary for cell
division are synthesized; this phase typically lasts several
hours. Lipid and carbohydrates are also synthesized
❑ Near the end of G1, a critical point termed the G1/S CHECKPOINT
holds the cell in G1 until the cell has all of the enzymes
necessary for the replication of DNA.
❑ After this checkpoint has been passed,THE CELL IS COMMITTED TO DIVIDE
❑ Before reaching the G1/S checkpoint, cells may exit from
the active cell cycle in response to regulatory signals and
pass into a nondividing phase called G0 , which is a
stable state during which cells usually maintain a
constant size. EXAMPLE: LIVER CELLS
❑ A cell in G0 maintains its specialized characteristics but
does not replicate its DNA or divide.
❑ From G0 , a cell may also proceed to mitosis and divide,
or die.
❑ Apoptosis may ensue if the cell’s DNA is so damaged
that cancer might result.
❑ G0, then, is when a cell’s fate is either decided or put on
hold.
❑ They can remain in G0 for an extended length of time,
even indefinitely, or they RE-ENTER G1 and the active cell
Spindle-
assembly Cells may enter
Mitosis and cytokinesis checkpoint Cytokinesis
(cdl dlvbiord take divdinq phase.
place in M phase.
Gt/M chekpoint
AfteF @R C
checkpoint, the G1 / S checkpoint
cdl can dude.
After the G1/S
checkpoint the
cell is
commited to
dividing
In G
, 2 the
prepares for mob.
DNA in S
S Phase
❑ After G1, the cell enters the S phase (for DNA SYNTHESIS ), in
which each chromosome duplicates.
❑ Although the cell is committed to divide after the G1/S
checkpoint has been passed, DNA synthesis must take
place before the cell can proceed to mitosis.
❑ If DNA synthesis is blocked (by drugs or by a mutation),
the cell will not be able to undergo mitosis.
❑ Before the S phase, each chromosome is unreplicated;
after the S phase, each chromosome is composed of two
chromatids.
❑ During S phase, the cell replicates its entire genome.
❑ As a result, each chromosome then consists of two
copies joined at an area called the CENTROMERE .
❑ In most human cells, S phase takes 8-10 HOURS .
❑ Many proteins are also synthesized during this phase,
including those that form the MITOTIC SPINDLE that will
pull the chromosomes apart.
G2
❑ After the S phase, the cell enters G2 (gap 2).
❑ In this phase, several additional biochemical events
necessary for cell division take place.
❑ TAKES PLACE BEFORE MITOTIC BUT AFTER DNA HAS BEEN
REPLICATED _ _ _ _ _ _ _
❑ More proteins are synthesized during this phase.
❑ Membranes are assembled from molecules made during
G1 and are stored as small, empty vesicles beneath the
plasma membrane.
❑ These vesicles will merge with the plasma membrane to
enclose the two daughter cells.
❑ The important _G2/M CHECKPOINT
_ _ __is reached near
the end of G2.
❑ This checkpoint is passed only if the cell’s DNA is
undamaged.
❑ Damaged DNA can inhibit the activation of some
proteins that are necessary for mitosis to take place.
❑ After the G2/M checkpoint has been passed, the cell is
ready to divide and enters the M phase.
❑ Although the length of interphase varies from cell type to
cell type, a typical dividing mammalian cell spends
about 10 hours in G1, 9 hours in S, and 4 hours in G2.
Mitosis
❑ As mitosis begins, the replicated chromosomes are
condensed enough to be visible, when stained, under a
microscope.
❑ The two long strands of identical chromosomal material
in a replicated chromosome are called chromatids.
❑ At a certain point during mitosis, a replicated
chromosome’s centromere splits, allowing its chromatid
pair to separate into two individual chromosomes.
(Although the centromere of a replicated chromosome
appears as a constriction, its DNA is replicated.)
a. b.
❑ Mitosis occurs in both haploid and diploid cells.
❑ Mitosis is conventionally broken down into five stages:
✓PROPHASE
✓PROMETAPHASE
✓METAPHASE
✓ ANAPHASE , and
✓TELOPHASE
NOTE: The disintegration of the nuclear membrane marks the starts of prometaphase
❑ Nonkinetochore microtubules—spindle microtubules that
do not bind to kinetochores—also originate from each
spindle pole and overlap in the middle of the spindle.
Metaphase
❑ During metaphase, the kinetochore microtubules orient
the chromosomes so that their centromeres become
aligned at the METAPHASE PLATE , a plane halfway
between the two spindle poles, with the long axes of the
chromosomes oriented at 90 degrees to the spindle axis.
❑ The centrosomes, now at opposite ends of the cell with
microtubules radiating outward and meeting in the
middle of the cell, center at the spindle poles.
❑ A SPINDLE-ASSEMBLY CHECKPOINT ensures that each
chromosome is aligned on the metaphase plate and
attached to spindle fibers from opposite poles.
❑ It had been accepted for many years that metaphase
chromosomes are the most condensed form of
chromosomes in mitosis (and meiosis).
❑ Recently, examination of 3D reconstructions of
microscope images of living mammalian cells taken with
high-power microscopes has revealed that further
chromosome condensation occurs just after the
chromosomes have finished separating in the subsequent
anaphase stage. This late condensation serves to
minimize the potential problem of chromosome arms
extending over the plane of division, which could result in
mechanical damage to the chromosomes.
Anaphase
❑ Anaphase begins suddenly when the COHESINS holding
together the sister chromatids of each chromosome are
cleaved by an enzyme called SEPARASE
❑ Once separated, the chromatids become full-fledged
chromosomes that move toward opposite ends of the cell.
❑ During anaphase, the joined centromeres of sister chromatids
separate, giving rise to two daughter chromosomes.
❑ Once the paired kinetochores on each chromosome
separate, the sister chromatid pairs undergo disjunction
(separation), and the daughter chromosomes move toward
the opposite poles.
❑ In anaphase, the daughter chromosomes are pulled toward
the opposite poles of the cell by the shortening microtubules
attached to the kinetochores.
❑ The microtubules that connect the chromosomes to the
spindle poles are composed of subunits of a protein
called TUBULIN
❑ Chromosome movement is due to the disassembly of
tubulin molecules at both the kinetochore end (called the
end) and the spindle end (called the end) of the spindle
fiber.
❑ Special proteins called MOLECULAR MOTORS disassemble tubulin
molecules from the spindle and generate forces that pull
the chromosome toward the spindle pole.
Telophase
❑ At the start of telophase, the two sets of daughter
chromosomes are assembled into two groups at opposite
ends of the cell.
❑ The chromosomes begin to uncoil and assume the
elongated state characteristic of interphase.
❑ A nuclear envelope forms around each group of
chromosomes, the spindle microtubules disappear, and
the nucleolus or nucleoli reform. A
❑ t this point, nuclear division is complete and the cell now
has two nuclei.
Cytokinesis
❑ Cytokinesis is DIVISION OF CYTOPLASM; usually, it follows the
nuclear division stage of mitosis and is completed by the
end of telophase.
❑ Cytokinesis compartmentalizes the two new nuclei into
separate daughter cells, completing mitosis and cell. In
animal cells, cytokinesis occurs by a process known as
CLEAVAGE
❑ The first sign of cleavage is the appearance of a
CLEAVAGE FURROW , a shallow groove in the cell surface
near the old metaphase plate.
❑ On the cytoplasmic side of the furrow is a contractile
ring of actin microfilaments associated with molecules of
the protein myosin.
❑ The actin microfilaments interact with the myosin
molecules, causing the ring to contract.
❑ The contraction of the dividing cell’s ring of
microfilaments is like the pulling of a drawstring.
❑ The cleavage furrow deepens until the parent cell is
pinched in two, producing two completely separated
cells, each with its own nucleus and its own share of
cytosol, organelles, and other subcellular structures.
Genetic Consequences of the Cell Cycle
❑ From a single cell, the cell cycle produces two cells that
contain the same genetic instructions.
❑ The resulting daughter cells are genetically identical with
each other and with their parent cell because DNA
synthesis in the S phase creates an exact copy of each
DNA molecule, giving rise to two genetically identical
sister chromatids.
❑ Mitosis then ensures that one of the two sister chromatids
from each replicated chromosome passes into each new
cell.
❑ Another genetically important result of the cell cycle is
that each of the cells produced contains a full
complement of chromosomes: there is no net reduction
or increase in chromosome number.
❑ Not all cells resulting from the cell cycle are identical in
their cytoplasmic content.
The Cell Cycle Clock: Cyclins and Cyclin-Dependent
Kinases
❑ Rhythmic fluctuations in the abundance and activity of
cell cycle control molecules pace the sequential events of
the cell cycle.
❑ These regulatory molecules are mainly proteins of two
types: protein kinases and cyclins.
❑ Protein kinases are enzymes that activate or inactivate
other proteins by phosphorylating them.
❑ Many of the kinases that drive the cell cycle are actually
present at a constant concentration in the growing cell,
but much of the time they are in an inactive form.
❑ To be active, such a kinase must be attached to a cyclin,
a protein that gets its name from its cyclically fluctuating
concentration in the cell.
❑ Because of this requirement, these kinases are called
cyclin-dependent kinases, or Cdks.
❑ The activity of a Cdk rises and falls with changes in the
concentration of its cyclin partner.
❑ MPF , the cyclin-Cdk complex, activity correspond to
the peaks of cyclin concentration.
❑ The cyclin level rises during the S and G2 phases and
then falls abruptly during M phase.
❑ The initials MPF stand for “maturation-promoting factor,”
but we can think of MPF as “M-phase-promoting factor”
because it triggers the cell’s passage into the M phase,
past the G2 checkpoint.
MPF
• Aids in nuclear membrane breakdown, spindle formation, and chromosome
condensation
❑ When cyclins that accumulate during G2 associate with
Cdk molecules, the resulting MPF complex phosphorylates
a variety of proteins, initiating mitosis.
❑ MPF acts both directly as a kinase and indirectly by
activating other kinases.
❑ During anaphase, MPF helps switch itself off by initiating
a process that leads to the destruction of its own cyclin.
❑ The noncyclin part of MPF, the Cdk, persists in the cell,
inactive until it becomes part of MPF again by
associating with new cyclin molecules synthesized during
the S and G2 phases of the next round of the cycle.
❑ Proteins known as cyclins (named because their
concentration increases and decreases in a regular
pattern through the cell cycle) and enzymes known as
cyclin-dependent kinases (Cdks) are the key
components in the regulatory events that occur at
checkpoints.
❑ At the G1-to-S checkpoint, two different G1 cyclin–Cdk
complexes form, resulting in activation of the kinases.
❑ The kinases catalyze a series of phosphorylations (addition
of phosphate groups) of cell cycle control proteins, affecting
the functions of those proteins and leading, therefore, to
transition into the S phase.
❑ A similar process occurs at the G2-to-M checkpoint.
❑ A cyclin binds to a Cdk to form a complex.
❑ Until the cell is ready to enter mitosis, phosphorylation of
the Cdk by another kinase keeps the Cdk inactive.
❑ At that time, a phosphatase removes the key phosphate
from the Cdk, activating the enzyme.
❑ Phosphorylations of proteins by the Cdk move the cell
into mitosis.
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Stop and Go Signs: Internal and External Signals at the
Checkpoints
❑ Animal cells generally have built-in stop signals that halt
the cell cycle at checkpoints until overridden by go-
ahead signals. (The signals are transmitted within the cell
by the kinds of signal transduction pathways)
❑ Many signals registered at checkpoints come from
cellular surveillance mechanisms inside the cell.
❑ These signals report whether crucial cellular processes
that should have occurred by that point have in fact
been completed correctly and thus whether or not the
cell cycle should proceed.
❑ Checkpoints also register signals from outside the cell.
❑ Three important checkpoints are those in G1, G2, and M
phases.
❑ For many cells, the G1 checkpoint—dubbed the
“restriction point” in mammalian cells—seems to be the
most important.
❑ If a cell receives a go-ahead signal at the G1
checkpoint, it will usually complete the G1, S, G2, and M
phases and divide.
❑ If it does not receive a go-ahead signal at that point, it
may exit the cycle, switching into a nondividing state
called the G0 phase.
❑ Most cells of the human body are actually in the G0
phase.
❑ Mature NERVE CELLS AND MUSCLE CELLS never divide.
❑ Other cells, such as liver cells, can be “called back” from
the G0 phase to the cell cycle by external cues, such as
growth factors released during injury.
Loss of Cell Cycle Controls in Cancer Cells
❑ Cancer cells do not heed the normal signals that regulate
the cell cycle.
❑ In culture, they do not stop dividing when growth factors are
depleted.
❑ A logical hypothesis is that cancer cells do not need growth
factors in their culture medium to grow and divide.
❑ They may make a required growth factor themselves, or they
may have an abnormality in the signaling pathway that
conveys the growth factor’s signal to the cell cycle control
system even in the absence of that factor.
❑ Another possibility is an abnormal cell cycle control system.
❑ In these scenarios, the underlying basis of the abnormality is
almost always a change in one or more genes (for example, a
mutation) that alters the function of their protein products,
resulting in faulty cell cycle control.
❑ If and when they stop dividing, cancer cells do so at random
points in the cycle, rather than at the normal checkpoints.
Cancer cells can go on dividing indefinitely in culture if they
are given a continual supply of nutrients; in essence, they are
“immortal.”
❑ A striking example is a cell line that has been reproducing in
culture since 1951, called HeLa cells because their original
source was a tumor removed from a woman named
Henrietta Lacks.
❑ Cells in culture that acquire the ability to divide indefinitely
are said to have undergone transformation, the process that
causes them to behave like cancer cells.
❑ By contrast, nearly all normal, nontransformed mammalian
cells growing in culture divide only about 20 to 50 times
before they stop dividing, age, and die.
❑ The abnormal cells may remain at the original site if they
have too few genetic and cellular changes to survive at
another site. In that case, the tumor is called a benign
tumor.
❑ Most benign tumors do not cause serious problems and
can be removed by surgery.
❑ In contrast, a malignant tumor includes cells whose
genetic and cellular changes enable them to spread to
new tissues and impair the functions of one or more
organs; these cells are also considered transformed cells.
MEIOSIS
• Also known as REDUCTION DIVISION
• From 46 chromosomes to 23 chromosomes
• Diploid to Haploid
• Sex cells
INTERPHASE PROPHASE I
• Cell growth • Leptonema = condensation of chromatids
• DNA replication • Zygonema = line up with their homologous pairs
• Cellular activities
• Pachynema = crossing over (transfer of genetic information
PPMAT I exchange it with each other that results to recombinant
PPMAT II chromosomes)
• Diplonema = synaptonemal complex begin to move apart
MEIOSIS
❑ Meiosis is the two successive divisions of a DIPLOID
nucleus after only one DNA replication (chromosome
duplication) cycle.
❑ The original diploid nucleus contains one haploid set of
chromosomes from the mother and one set from the
father.
❑ It results in the formation of haploid gametes (eggs and
sperm by gametogenesis);
❑ Before meiosis, the DNA that makes up homologous
chromosomes replicates, and during meiosis these
chromosomes pair and then undergo two divisions-
meiosis I and meiosis II—each consisting of a series of
stages.
❑ MEIOSIS I results in a reduction in the number of
chromosomes in each cell from diploid to haploid
(reductional division—each resulting pair of attached
sister chromatids counts as a single chromosome)
❑ MEIOSIS II results in the separation of the sister chromatids.
❑ In most cases, the divisions are accompanied by
cytokinesis, so the meiosis of a single diploid cell
produces HAPLOID CELLS
Meiosis I: The First Meiotic Division
❑ Meiosis I, in which the chromosome number is
reduced from diploid to haploid, consists of five
stages:
✓PROPHASE
✓PROMETAPHASE ,
✓METAPHASE ,
✓ANAPHASE and
✓TELOPHASE
Prophase I
❑ When prophase I begins, the chromosomes have already
duplicated, with each consisting of two sister chromatids
attached at a centromere.
❑ Prophase I is divided into a number of substages.
❑ Prophase I of meiosis is similar to prophase of mitosis.
❑ The important difference between prophase I of meiosis
and prophase of mitosis is that homologous
chromosomes pair with each other in meiosis, and
crossing-over occurs only in meiosis.
❑ In leptonema (early prophase I, the LEPTOTENE STAGE
), the extended chromosomes begin to condense and
become visible as long, thin threads.
❑ Once a cell enters leptonema, it is committed to the
meiotic process.
❑ In zygonema (early to middle prophase I, the
ZYGOTENE stage), the chromosomes continue to
condense.
❑ The homologous pairs of chromosomes actively find
each other and align roughly along their lengths.
❑ Each pair of homologs then undergoes SYNAPSIS —the
formation along the length of the chromatids of a
zipperlike structure called the SYNAPTONEMAL COMPLEX which
aligns the two homologs precisely, base pair for base pair.
❑ Pachynema (middle prophase I, the PACHYTENE ) starts
when synapsis is completed.
❑ Because of the replication that occurred earlier, each
synapsed set of homologous chromosomes consists of
four chromatids and is called a bivalent or a tetrad.
❑ During pachynema, a most significant event for genetics
occurs: CROSSING OVER —the reciprocal physical exchange
of chromosome segments at corresponding positions
along pairs of homologous chromosomes.
❑ The positions at which crossing-over occur along the
chromosomes are largely random, and vary from one
meiosis to another.
❑ The physical exchange that occurs in crossing-over is
facilitated by the alignment of the homologous
chromosomes brought about by the synaptonemal
complex.
❑ If there are genetic differences between the homologs,
crossing-over can produce new gene combinations in a
chromatid.
❑ There is usually no loss or addition of genetic material to
either chromosome, since crossing-over involves reciprocal
exchanges.
❑ A chromosome that emerges from meiosis with a
combination of alleles that differs from the combination
with which it started is called a RECOMBINANT CHROMOSOMES .
❑ Therefore, crossing-over is a mechanism that can give
rise to genetic recombination.
❑ At the end of pachynema, the synaptonemal complex is
disassembled, and the chromosomes have started to
elongate.
❑ In diplonema (middle to late prophase I, the DIPLOTENE )
the synaptonemal complex disassembles and the
homologous chromosomes begin to move apart.
❑ The result of crossing-over becomes visible during
diplonema as a cross-shaped structure called a chiasma
(plural, chiasmata).
❑ At each chiasma, the homologous chromosomes are
very tightly associated.
❑ Because all four chromatids may be involved in crossing-
over events along the length of the homologs, the
chiasma pattern at this stage may be quite complex.
❑ In DIAKINESIS (late prophase I), the chromosomes
condense even more, making it now possible to see the
four members of the tetrads.
❑ The chiasmata are clearly visible at this stage.
Prometaphase I
❑ In prometaphase I, NUCLEOLI DISAPPEARS , the nuclear envelope
breaks down, and the meiotic spindle that has been
forming between the separating centriole pairs enters the
former nuclear area.
❑ As in mitosis, kinetochore microtubules attach to the
chromosomes; that is, kinetochore microtubules from one
pole attach to both sister kinetochores of one duplicated
chromosome, and kineteochore microtubules from the
other pole attach to both sister kinetochores of the other
duplicated chromosome in a tetrad.
❑ Nonkinetochore microtubules from each pole overlap in
the center of the cell.
Metaphase I
❑ In metaphase I, the kinetochore microtubules align the
tetrads on the METAPHASE PLATE
❑ Importantly, the pairs of homologs (the tetrads) are found
at the metaphase plate.
❑ In contrast, in mitosis, replicated homologous
chromosomes (sister chromatid pairs) align independently
of one another at the metaphase plate.
Anaphase I
Prometaphase II
❑ In prometaphase II, the NUCLEAR ENVELOPE BREAKDOWN
(if formed in telophase I) break down, and the spindle
organizes across the cell.
❑ Kinetochore microtubules from the opposite poles attach
to the kinetochores of each chromosome.
Metaphase II
❑In metaphase II, the movement of the kinetochore
microtubules aligns the chromosomes on the METAPHASE PLATE
Anaphase II
❑ During anaphase II, the centromeres separate, and the now-
daughter chromosomes are pulled to the opposite poles of
the spindle.
❑ One sister chromatid of each pair goes to one pole, and the
other goes to the opposite pole.
❑ The separated chromatids are now considered chromosomes
in their own right.
Telophase II
❑ In the last stage, telophase II, the chromosomes begin
decondensing, a nuclear envelope forms around each set of
chromosomes, and cytokinesis takes place.
❑ After telophase II, the chromosomes continue
DECONDENSATE , eventually becoming invisible under the light
microscope.
❑ The end products of the two meiotic divisions are four
haploid cells (gametes in animals) from one original
diploid cell.
❑ Each of the four progeny cells has one chromosome
from each homologous pair of chromosomes.
❑ Because of crossing-over, these chromosomes are not
exact copies of the original chromosomes.
A Comparison of Mitosis and Meiosis
❑ Basically, meiosis reduces the number of chromosome
sets from two (diploid) to one (haploid), whereas mitosis
conserves the number of chromosome sets.
❑ Therefore, meiosis produces cells that differ genetically
from their parent cell and from each other, whereas
mitosis produces daughter cells that are genetically
identical to their parent cell and to each other.
Three events unique to meiosis occur during meiosis I:
1. SYNAPSIS AND CROSSING OVER
❑ During prophase I, duplicated homologs pair up and
crossing over occurs.
❑ Synapsis and crossing over normally do not occur during
prophase of mitosis.
2. HOMOLOGOUS PAIR AT METAPHASE PLATE
❑ At metaphase I of meiosis, chromosomes are positioned
at the metaphase plate as pairs of homologs, rather than
individual chromosomes, as in metaphase of mitosis.
3. SEPARATION OF HOMOLOGOUS .
❑ At anaphase I of meiosis, the duplicated chromosomes
of each homologous pair move toward opposite poles,
but the sister chromatids of each duplicated
chromosome remain attached.
❑ In anaphase of mitosis, by contrast, sister chromatids
separate.
❑Meiosis I is called the REDUCTIONAL DIVISION because it
reduces the number of chromosome sets from two (diploid) to
one (haploid).
❑ During meiosis II (the EQUATIONAL DIVISION), sister
chromatids separate, producing haploid daughter cells.
❑ The mechanism for separating sister chromatids is virtually
identical in meiosis II and mitosis.
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