The cell cycle

The cell cycle, or cell-division cycle, is the series of events that takes place in a
cell leading to its division and duplication (replication). In cells without a nucleus
(prokaryotic), the cell cycle occurs via a process termed binary fission. In cells
with a nucleus (eukaryotes), the cell cycle can be divided in three periods
(stages):
INTERPHASE during which the cell grows, accumulating nutrients needed for
mitosis and duplicating its DNA
MITOSIS - during which the cell splits itself into two distinct cells, often called
"daughter cells"
CYTOKINESIS - during which the new cell is completely divided.

State

Phase

quiescen
t/
Gap 0
senesce
nt

Interpha
se

Abbrevia
tion

Description

G0

A resting phase where the cell has left the cycle and has
stopped dividing.

Gap 1

G1

Cells increase in size in Gap 1. The G1 checkpoint control

mechanism ensures that everything is ready for DNA
synthesis.

Synthe
sis

DNA replication occurs during this phase.

G2

During the gap between DNA synthesis and mitosis, the cell
will continue to grow. The G2 checkpoint control mechanism
ensures that everything is ready to enter the M (mitosis)
phase and divide.

Cell growth stops at this stage and cellular energy is focused

on the orderly division into two daughter cells. A checkpoint in
the middle of mitosis (Metaphase Checkpoint) ensures that
the cell is ready to complete cell division.

Gap 2

Cell
Mitosis
division

Interphase
The first stage of the cell cycle is interphase. Before a dividing cell enters mitosis,
it undergoes a period of growth called interphase. Approximately 90 percent of a
cell's time in the normal cellular cycle may be spent in interphase.

Interphase consists of three stages: G1 (first gap), S (Synthesis), and G2 (second

gap).
G1 phase: The period prior to the synthesis of DNA. In this phase, the cell
increases in mass in preparation for cell division. This phase is marked by
synthesis of various enzymes that are required in S phase, mainly those
needed for DNA replication.
S phase: The period during which DNA is synthesized. Each chromosome now
consists of two sister chromatids. The amount of DNA in the cell has doubled.
G2 phase: The period after DNA synthesis has occurred but prior to the start of
prophase. The cell synthesizes proteins and continues to increase in size.
Metabolic changes assemble the cytoplasmic materials necessary for mitosis
and cytokinesis.
Resting (G0 phase)
The term "post-mitotic" is sometimes used to refer to both quiescent and
senescent cells. Nonproliferative cells in multicellular eukaryotes generally enter
the quiescent G0 state from G1 and may remain quiescent for long periods of time,
possibly indefinitely (as is often the case for neurons). Cellular senescence is a
state that occurs in response to DNA damage or degradation that would make a
cell's progeny nonviable; it is often a biochemical alternative to the self-destruction
of such a damaged cell by apoptosis.
The second stage of the cell cycle is mitosis.
Mitosis (M Phase/Mitotic phase)
Mitosis is the process by which a eukaryotic cell separates the chromosomes in
its cell nucleus into two identical sets, in two separate nuclei. It is generally
followed immediately by cytokinesis, which divides the nuclei, cytoplasm,
organelles and cell membrane into two cells containing roughly equal shares of
these cellular components. This accounts for approximately 10% of the cell cycle.
Prokaryotic cells, which lack a nucleus, divide by a process called binary fission.
Errors in mitosis can either kill a cell through apoptosis or cause mutations that
may lead to cancer.
Mitosis consists of five stages: prophase, prometaphase, metaphase, anaphase
and telophase, and cytokinesis (strictly speaking, cytokinesis is not part of mitosis
but is an event that directly follows mitosis in which cytoplasm is divided into two
daughter cells).
Prophase

Prophase occupies over half of mitosis. Normally, the genetic material in the
nucleus is in a loosely bundled coil called chromatin. At the onset of prophase,
chromatin condenses together into a highly ordered structures called
chromosomes (which are observable under a microscope), the nucleolus
disappears, the nuclear membrane begins to break down, the chromosomes
appear as two identical chromatids joined together, and the mitotic spindle begins
to form. Each replicated chromosome consists of two identical chromatids (or
sister chromatids) held together by a structure known as the centromere with
the help by the cohesin protein complex.
Close to the nucleus are structures called centrosomes, which are made of a pair
of centrioles found in most eukaryotic animal cells. Centrosome duplicates itself
and two daughter centrosomes migrate to opposite ends of the cell. The
centrosomes organise the production of microtubules that form the mitotic
spindle.
Prometaphase
In the prometaphas stage, the nuclear envelope disassembles and microtubules
invade the nuclear space. This is called open mitosis, and it occurs in most
multicellular organisms.
The chromosomes, led by their centromeres, migrate to the equatorial plane in the
cell. The microtubules extend from each centrosome toward the middle of the cell
and begin to attach to the chromatids. The mitotic spindle fibres bind to a
kinetochore complex protein structure on each side of the centromere. Energy
from ATP is used.
Metaphase
During metaphase, the centrosomes are at opposite ends of the cell, the
chromosomes align in the middle of the cell, at a site known as the equatorial
plane - an imaginary line that is equidistant from the two centrosome poles.
Microtubules find and attach to kinetochores in prometaphase. Then the two
centrosomes start pulling the chromosomes through their attached centromeres
towards the two ends of the cell. As a result, the chromosomes come under
longitudinal tension from the two ends of the cell. At this phase all chromosomes
are very good visible even with the light microscope, because are situated on the
surface called metaphase plate.
Anaphase
Anaphase is the shortest stage of Mitosis. This stage begins with the centromeres
division, and the sister chromatids of each chromosome being pulled apart (or
disjoin) because the proteins that bind sister chromatids together are cleaved,
thus forming a daughter chromosome (that is separated sister chromatids are

now referred to as daughter chromosomes) composed of one chromatid. At the

end of anaphase, the cell has succeeded in separating identical copies of the
genetic material into two distinct populations.
Telophase
The last stage of Mitosis is Telophase and is a reversal of many of the processes
observed during prophase. The the two nuclei begin to form in the cell. A new
nuclear envelope, using fragments of the parent cell's nuclear membrane, forms
around each set of separated sister chromosomes, the chromosomes uncoil and
become less condensed, and the spindle fibres disappear. Both sets of
chromosomes, now surrounded by new nuclei, unfold back into chromatin. Mitosis
is complete, but cell division is not yet complete.
Cytokinesis
The final stage of the cell cycle is cytokinesis - a separate process that begins at
the end of anaphase, and further run during telophase. Cytokinesis is the division
of the cytoplasm. Two daughter cells are then formed by spliting a binucleate cell
into two. Citokinesis differs in plant and animal cells.
Cytokinesis in Animal Cells
Animal cell cytokinesis begins shortly after the onset of sister chromatid
separation in the anaphase. A contractile ring, made of non-muscle myosin II and
actin filaments, assembles in the middle of the cell. Use ATP hydrolysis energy to
form a cleavage furrow. Cleavage furrow ingresses (moves inwards), and
ingression continues until a so-called snear or loop constricts the cell and divides
into two.
Cytokinesis in Plant Cells
Due to the presence of a cell wall, cytokinesis in plant cells is significantly different
from that in animal cells. Plant cells construct a cell plate in the middle of the cell:
(1) creation of the phragmoplast, an array of microtubules that guides and
supports the formation of the cell plate;
(2) trafficking of vesicles to the division plane and their fusion to generate a
tubular-vesicular network; The Golgi apparatus produces vesicles , which move
along microtubules to the middle of the cell where they fuse to form the cell plate
followed by deposition of cellulose and other cell wall components. The cell plate
expands until the cytoplasm is divided separating the two nuclei.
The end of cytokinesis marks the end of the M-phase.

The cell then enters interphase - the interval between mitotic divisions.

Significance
Mitosis is important for the maintenance of the chromosomal set; each cell formed
receives chromosomes that are alike in composition and equal in number to the
chromosomes of the parent cell.
Following are the occasions where mitosis happens:

Development and growth

Cell replacement
Regeneration
Asexual reproduction

Consequences of errors
Although errors in mitosis are rare, the process may go wrong, especially during
early cellular divisions in the zygote. Mitotic errors can be especially dangerous to
the organism because future offspring from this parent cell will carry the same
disorder.
Occasionally when cells experience nondisjunction, they fail to complete cell
division and retain both nuclei in one cell, resulting in binucleated cells.
The Cell-Cycle Control System
The most basic control system should possess the following features:
A clock, or timer, that turns on each event at a specific time, thus
providing a fixed amount of time for the completion of each event.
A mechanism for initiating events in the correct order; entry into mitosis,
for example, must always come after DNA replication.
A mechanism to ensure that each event is triggered only once per cycle.
Binary (on/off) switches that trigger events in a complete, irreversible
fashion. It would clearly be disastrous, for example, if events like
chromosome condensation or nuclear envelope breakdown were
initiated but not completed.
Robustness: backup mechanisms to ensure that the cycle can work
properly even when parts of the system malfunction.

 Adaptability, so that the system's behavior can be modified to suit

specific cell types or environmental conditions.
In most cells there are several points in the cell cycle, called checkpoints, at which
the cycle can be arrested if previous events have not been completed.
Checkpoints are important in another way as well. They are points in the cell cycle
at which the control system can be regulated by extracellular signals from other
cells.
The central components of the cell-cycle control system are cyclin-dependent
protein kinases (Cdks), whose activity depends on association with regulatory
subunits called cyclins.
A simplified view of the core of the cell-cycle control system
Cdk associates successively with different cyclins to trigger the different events of
the cycle. Cdk activity is usually terminated by cyclin degradation. For simplicity,
only the cyclins that act in S phase (S-cyclin) and M phase (M-cyclin) are shown,
and they interact with a single Cdk; as indicated, the resulting cyclin-Cdk
complexes are referred to as S-Cdk and M-Cdk, respectively.
There are four classes of cyclins, each defined by the stage of the cell cycle at
which they bind Cdks and function. Three of these classes are required in all
eucaryotic cells:
1.G1/S-cyclins bind Cdks at the end of G1 and commit the cell to DNA
replication.
2.S-cyclins bind Cdks during S phase and are required for the initiation of DNA
replication.
3.M-cyclins promote the events of mitosis.
In most cells, a fourth class of cyclins, the G1-cyclins, helps promote passage
through Start or the restriction point in late G1.
Cyclin-Cdk complexes can also be regulated by the binding of Cdk inhibitor
proteins (CKIs). There are a variety of CKI proteins, and they are primarily
employed in the control of G1 and S phase. The three-dimensional structure of a
cyclin-Cdk-CKI complex reveals that CKI binding dramatically rearranges the
structure of the Cdk active site, rendering it inactive