Cell cycles - Chapter 9

Regeneration : Existing skin cells migrate to close

the wound and prevent bleeding. Then cells just
under the new skin transform into “regeneration
cells” that form a temporary tissue called
a blastema. Blastema cells exhibit two important
characteristics: (1) they reenter the cell cycle and
divide up to 50 times faster than usual, and (2)
they expand their previously restricted range
of function. The blastema provides large numbers
of daughter cells capable of maturing into new
bone, nerve, muscle, and blood vessel cells in
response to signal proteins produced by the skin.
Although regenerating lost fins is dramatic,
zebrafish can also regenerate lost heart muscle.
Studies are under way to explore the possibility
that human hearts could be stimulated to repair
themselves following heart attack damage rather
than just form scar tissue.
If the cell is from inside the cheek of a moose or
from a yellow rose petal, the future may hold
neither growth nor cell division. In fact, some
cells may even be programmed to die
immediately!
Before dividing, most cells enter a period of
growth in which they synthesize proteins, lipids,
and carbohydrates and (during one particular
stage) replicate their nuclear DNA. After this
growth period, the nuclei divide, and, usually,
cytokinesis (the division of the cytoplasm) follows,
partitioning nuclei to each of two
daughter cells. Each daughter nucleus contains a
copy of the original DNA. This sequence of
events--a period of growth followed by nuclear
division and cyto- kinesisis known as the
cell cycle.
At a certain stage of the life cycle of sex ually
reproducing organisms, some cells are needed
that are decidedly different from the parent cells.
A different type of cell division process is
required. Meiosis is a special type of cell division,
produces the necessary daughter nuclei--different
in that they have only half the number of
chromosomes as the parental nuclei that began
the process. Also, many of the genetic traits
carried by these daughter nuclei are in different
combinations from those of the parent cell. The
cells that are the products of meiosis may
function as gametes in animals (fusing with other
gametes to make a zygote) and as spores in plants
and many fungi (dividing by mitosis).
DNA in Eukaryotes :
In all eukaryotes, the hereditary information of
the nucleus is distributed among several linear
DNA molecules. These DNA molecules are
combined with proteins, that stabilize the DNA,
assist in pack- aging DNA during cell division,
and influence the expression of individual genes.
Each chromosome in a cell is composed of one of
these linear DNA molecules along with its
associated proteins.
Chromosomes are the nuclear units of genetic
information that are divided and distributed by
mitotic cell division.
Most eukaryotes have two copies of each type of
chromosome in their nuclei, and their
chromosome complement is said to be diploid, or
2n. For example, humans have 23 different pairs
of chromosomes for a diploid number of 46
chromosomes (2n = 46). Other eukaryotes, mostly
microorganisms, may have only one copy of each
type of chromosome in their nucleus, so their
chromosome complement is said to
be haploid. Baker’s yeast (Saccharomyces
cerevisiae) is an example of an organism that can
grow as a diploid (2n = 32) and as a haploid (n
= 16). Still others, such as many plant species,
have three, four, or even more complete sets of
chromosomes in each cell. The number of
chromosome sets is called the ploidy of a cell
or species.
Replication of the DNA of each individual
chromosome creates two identical molecules
called sister chromatids. Newly formed sister
chromatids are held together until mitosis
separates them, placing one in each of the two
daughter nuclei. As a result of this precise
division, each daughter nucleus receives exactly
the same number and types of chromosomes, and
con- tains the same genetic information, as the
parent cell entering the division. The equal
distribution of daughter chromosomes to each of
the two cells that result from cell division is called
chromosome segregation.
The precision of chromosome replication and
segregation in the mitotic cell cycle creates a
group of cells called a clone. Except for rare
chance muta- tions, all cells of a clone are
genetically identical. Since all the diverse cell
types of a complex multicel- lular organism arose
by mitosis from a single zygote, they should all
contain the same genetic information.
If we choose to let the formation of a new
daughter cell mark the beginning of the mitotic
cell cycle, then the first and longest phase
is interphase. During interphase, the cell grows
and replicates its DNA in preparation for mitosis
(also called the M phase) and cytokinesis.
Interphase Extends from the End of One Mitosis
to the Beginning of the Next Mitosis . Interphase
begins as a daughter cell from a previous division
cycle enters an initial period of
cytoplasmic growth. During this initial growth
stage, called the G1 phase of the cell cycle, the cell
makes various RNAs, proteins, and other types of
cellular molecules but not nuclear DNA (the G in
G1 stands for gap, referring to the absence of
DNA synthesis). Then, if the cell is going to
divide, DNA replication begins, initiating the S
phase of the cell cycle (S stands for synthesis,
meaning DNA synthesis). During the S phase, the
cell duplicates the chro- mosomal proteins as well
as the DNA and continues the synthesis of other
cellular molecules. As the S phase is completed,
the cell enters the G2 phase of the cell cycle (G2
refers to the second gap during which there is no
DNA synthesis). During G2, the cell continues to
synthesize RNAs and proteins, including those
required for mitosis, and the cell continues
to grow. At the end of G2, which marks the end
of inter- phase, mitosis begins. During all the
steps of inter- phase, the chromosomes are
relatively loose, but organized, in the nucleus .
Usually, G1 is the only phase of the cell cycle that
varies in length for a given species. Thus, whether
cells divide rapidly or slowly primarily depends
on the length of G1. Once DNA replica- tion
begins, most mammalian cells take about 10 to 12
hours to proceed through the S phase, about 4 to
6 hours to go through G2, and about 1 to 4 hours
to complete mitosis. G1 is also the stage in which
many cell types stop dividing. This state of divi-
sion arrest is often designated the G0 phase . For
example, in humans, cells of the nervous system
normally enter G0 once they are fully mature.
The events of interphase are an important focus
of research, par- ticularly the regulatory controls
for the transition from the G1 phase to G2 Period
after DNA replicates; cell prepares for division S
Period when DNA replicates and chromosomal
proteins are duplicated G1 Period of cell growth
before the DNA replicates the S phase and,
with it, the com- mitment to
cell division. Understanding the molec- ular
events that regulate the G /S phase transition is
important because one of the hallmarks of cancer
is the loss of normal control of that transition.
• In mitotic cell division, DNA replication is
followed by the equal separation--that is,
segregation--of the replicated DNA mol- ecules
and their delivery to daughter cells. The process
ensures that the two cell products of a division
have the same genetic information as the parent
cell entering division.
• Mitosis is the basis for growth and maintenance
of body mass in multicelled eukaryotes and for
the reproduction of many single-
celled eukaryotes.
• The chromosomes of eukaryotic cells are
individual, linear DNA molecules with
associated proteins.
• DNA replication and the duplication of
chromosomal proteins convert each chromosome
into a structure composed of two exact copies
known as sister chromatids.
The Mitotic Cell Cycle
The interphase and mitosis, together constitute
the mitotic cell cycle.
Mitosis occurs in five stages.
• In prophase (stage 1), the chromosomes
condense into short rods and the spindle forms in
the cytoplasm.
• In prometaphase (stage 2), the nuclear envelope
breaks down, the spindle enters the former
nuclear area, and the sister chromatids of each
chromosome make connections to opposite
spindle poles. Each chromatid has a kinetochore
that attaches to spindle microtubules .
• In metaphase (stage 3), the spindle is fully
formed and the chromosomes, moved by the
spindle micro- tubules, become aligned at the
metaphase plate .
• In anaphase (stage 4), the spindle separates the
sister chromatids and moves them to opposite
spindle poles. At this point, chromosome
segregation is com- plete .
• In telophase (stage 5), the chromosomes starts
decondensing .As decondensation proceeds, the
nucleolus reappears, RNA
transcription resumes, and a new nuclear
envelope forms around the chromosomes at each
pole, producing the two daughter nuclei. At this
point, nuclear division is complete, and the cell
has two nuclei
• Cytokinesis, the division of the cytoplasm,
usually follows the nuclear division stage of
mitosis and pro- duces two daughter cells, each
containing one of the daughter nuclei. In most
cells, cytokinesis begins during telophase or even
late anaphase. By the time cytokinesis is
completed, the daughter nuclei have progressed
to the interphase stage and entered the G1 phase
of the next cell cycle.
• Cytokinesis in animal cells proceeds by
furrowing, in which a band of microfilaments
just under the plasma membrane contracts,
gradually separating the cyto- plasm into
two parts .
• In plant cytokinesis, cell wall material is
deposited along the plane of the former
spindle midpoint; the deposition continues until a
continuous new wall, the cell plate, separates the
daughter cells.
Animal cells and many protists have a
centrosome, a site near the nucleus from which
microtubules radiate outward in all
directions.The centrosome is the main
microtubule organizing centre (MTOC) of the
cell, anchoring the microtubule cytoskeleton
during interphase and positioning many of the
cytoplasmic organelles. The centrosome contains
a pair of centrioles, usually arranged at right
angles to each other. Although centrioles
originally appeared to be important in the
construction of the mitotic spindle, it has now
been shown that they can be removed with no ill
effect. The primary function of centrioles is
actually to generate the microtubules needed for
flagella or cilia, the whiplike extensions that
provide cell motility.
When DNA replicates during the S phase of the
cell cycle, the centrioles within the centrosome
also dupli- cate, producing two pairs of
centrioles(step 2).
As prophase begins in the M phase, the centro-
some separates into two parts (step 3).
The duplicated centrosomes, with the centrioles
inside them, continue to separate until they reach
opposite ends of the nucleus (step 4).
As centrosomes move apart, the microtubules
between them lengthen and increase in number.
Cyclins and Cyclin-Dependent Kinases Are the
Internal Controls that Directly Regulate Cell
Division Cyclin-dependent kinases (CDK) are
major players in the regulation of cell
division, directly affecting progression through
the cell cycle. CDKs are protein kinases, enzymes
that add phosphate groups to target
proteins. CDK enzymes are called “cyclin
dependent” because they are “switched on” only
when combined with another protein called a
cyclin. Since the con- centration of the cyclins
rises and falls during the cell cycle, so does the
enzyme activity of the CDKs (even though the
concentration of CDK proteins remains
constant). The name cyclin reflects these cyclic
fluc- tuations in its concentration. CDK
combinations regu- late cell cycle transitions at
different “checkpoints.”As part of the internal
controls, the cell cycle has built-in checkpoints to
prevent critical phases from beginning until the
previous phases are completed.
Formation and Action of the Mitotic Spindle
• In animal cells, the centrosome divides and the
two parts move apart. As they do so, the
microtubules of the spindle form between them.
In plant cells with no centrosome, the spindle
microtubules assemble around the nucleus.
• In the spindle, kinetochore microtubules run
from the poles to the kinetochores of the
chromosomes, and nonkinetochore microtubules
run from the poles to a zone of overlap at the
spindle midpoint without connecting to the
chromosomes.
• During anaphase, the kinetochores move along
the kinetochore microtubules, pulling the
chromosomes to the poles. The nonkinetochore
microtubules slide over each other, pushing the
poles farther apart .
Cell Cycle Regulation
• The cell cycle is controlled directly by
complexes of cyclins and a cyclin-dependent
protein kinase (CDK). A CDK is activated when
combined with a cyclin and then adds phosphate
groups to target proteins, acti- vating them. The
activated proteins trigger the cell to progress to
the next cell cycle stage. Each major stage of the
cell cycle begins with activation of one or more
cyclin: CDK complexes and ends with
deactivation of the complexes by breakdown of
the cyclins.
• Important internal controls create checkpoints
to ensure that the reactions of one stage are
complete before the cycle proceeds to the next
stage.
• External controls are based primarily on
surface receptors that recognize and bind signals
such as peptide hormones and growth factors,
surface groups on other cells, or molecules of the
extracellular matrix. The binding triggers
internal reactions that speed, slow, or stop cell
division.
• Most cells in multicellular eukaryotes
progressively lose the ability to divide over time
by a process called cellular senescence. Factors
that contribute to senes- cence include
accumulating DNA damage and short- ening
telomeres.
• In cancer, control of cell division is lost and cells
divide continuously and uncontrollably, forming
a rapidly growing mass of cells that interferes
with body functions. Cancer cells also break loose
from their original tumour (metastasize) to form
additional tumours in other parts of the body.
• Certain cells may undergo programmed cell
death called apoptosis. Such a fate would be
appropriate for cells that are, for instance,
surplus for develop- ment, damaged, infected, or
functional only after death.
• Replication of the bacterial chromosome begins
at a site called the “origin” through reactions
catalyzed by enzymes located in the middle of the
cell. Once the origin of replication is duplicated,
the two origins migrate to the two ends of the
cells. Division of the cytoplasm then occurs
through a partition of cell wall material that
grows inward until the cell is separated into two
parts .
Cell-surface receptors in animal cells also rec-
ognize contact with other cells or with molecules
of the extracellular matrix. The contact triggers
internal reaction pathways that inhibit division
by arresting the cell cycle, usually in the G1
phase. The response, called contact inhibition,
stabilizes cell growth in fully developed organs
and tissues. As long as the cells of most tissues are
in contact with one another or with the
extracellular matrix, they are shunted into the G0
phase and prevented from dividing. If the con-
tacts are broken, the freed cells often enter
rounds of division
Normal human skin cells eventually stopped
dividing when grown in artificial culture. This
loss of proliferative ability over time is called cel-
lular senescence, and scientists have been
searching for the “Hayflick factors” that are
responsible for it. We consider two candidates:
DNA damage and tel- omere shortening.
Telomeres are repetitive DNA sequences that are
added to the ends of chromosomes by the enzyme
telomerase. Since DNA replication machinery is
unable to replicate the entire ends of linear
chromosomes, telomere sequence is lost at each
round of replica- tion. Once telomeres diminish
to a certain minimum length, cells stop dividing
(senesce) and may die.

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