8.

0 CELL CYCLE
8.1 Objectives
At the end of this topic you should be able to:
1. Describe the main events of each stage of the cell cycle.
2. Describe the stages of mitosis with emphasis on the chromosomal behaviour
at each stage.
3. Describe the stages of meiosis with emphasis on the chromosomal behaviour
at each stage.
4. Explain the significance of mitosis.
5. Explain the significance of meiosis.
6. Explain the difference between the events of mitosis and meiosis.

8.2 Introduction
All cells are produced by division of pre-existing cells. Continuity of life depends on
cell division. A cell born after cell division, proceeds to grow by macromolecular
synthesis, reaches a species-determined size and divides. Somatic cells (cells that form
a part of the body) divide by mitosis, while production of gametes (sex cells) is
achieved by the process of meiosis, which reduces the number of chromosomes to half
the normal number. Meiosis ensures that the number of chromosomes in the offspring
will be same as in their parents.

8.2.1 The cell cycle

The cell cycle involves the following three cycles.
(i) Chromosome cycle. In this DNA synthesis alternates with mitosis (or
karyokinesis or nuclear division). During DNA synthesis, each double-helical
DNA molecule is replicated into two identical daughter DNA molecules and
during mitosis the duplicated copies of the genome are ultimately separated.
(ii) Cytoplasmic cycle. In this cell growth alternates with cytokinesis (or
cytoplasmic division). During cell growth many other components of the cell
(RNA, proteins and membranes) become double in quantity and during
cytokinesis the cell as a whole divide into two. Usually the karyokinesis is

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 followed by the cytokinesis but sometimes the cytokinesis does not follow the
karyokinesis and results into the multinucleate cell.
(iii) Centrosome cycle. Both of the above cycles require that the centrosome be
inherited reliably and duplicated precisely in order to form the two poles of the
mitotic spindle.

The cell cycle is divided into four phases or stages: G1, S, G2 and M phase. The G1
phase, S phase and G2 phase are combined to form the interphase (Figure 8.1).
(i) G1 phase. After the M phase of previous cell cycle, the daughter cells begin
G1 of interphase of new cell cycle. G1 is the resting phase. It is called first gap
phase since no DNA synthesis takes place during this stage. It is also called the
first growth phase, since it involves the synthesis of RNA, proteins and
membranes which lead to the growth of the nucleus and cytoplasm of each
daughter cell towards their mature size.
During G1 phase chromatin is fully extended and distinguishable as discrete
chromosomes with the light microscope. Metabolism activities which had
slowed down during the previous cell division are resumed during this stage.
G1 phase involves transcription of three types of RNAs, namely rRNA, tRNA
and mRNA. The rRNA synthesis is indicated by the appearance of the
nucleolus in the interphase (G1 phase) nucleus. Proteins synthesized during G1
phase are:
(a) regulatory proteins which control various events of mitosis;
(b) enzymes (e.g., DNA polymerase) necessary for DNA synthesis of the
next stage;
(c) tubulin and other mitotic apparatus proteins.
The duration of G1 phase is most variable. It either occupies 30 to 50 percent
of the total time of the cell cycle or lacks completey in the rapidly dividing
cells. Terminally differentiated somatic cells (i.e., end cells such as neurons
and striated muscle cells) that no longer divide are arrested usually in the G1
stage; such a type of G1 phase is called G0 phase.
(ii) S phase. During the S phase or synthetic phase of interphase, replication of
DNA and synthesis of histone proteins takes place. New histones are required

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 in massive amounts immediately at the beginning of the S period of DNA
synthesis to provide the new DNA with nucleosomes. Thus at the end of S
phase each chromosome has two DNA molecules and a duplicate set of genes.
S phase occupies roughly 35 to 45 percent of cell cycle.
(iii) G2 phase. This is a second gap or growth phase or resting phase of
interphase. During G2 phase synthesis of RNA and proteins continues which is
required for cell growth. It may occupy 10 to 20 percent time of cell cycle. As
the G2 phase draws to a close, the cell enters the M phase.

8.2.1.1. General events of the interphase

The interphase is characterised by the following events:
 The nuclear envelope remains intact.
 The chromosomes occur in the form of diffused, long, coiled and
indistinctly visible chromatin fibres.
 The DNA amount becomes double.
 Due to accumulation of ribosomal RNA (rRNA) and ribosomal proteins
in the nucleolus, the size of the latter is greatly increased.
 In animal cells, a daughter pair of centrioles originates near the already
existing centrioles and, thus, an interphase cell has two pairs of
centrioles.
 In animal cells, net membrane biosythesis increases just before cell
division (mitosis).
8.2.2. MITOSIS (M phase)
The mitosis (Greek, mitos=thread) occurs in somatic cells and it is meant for
multiplication of cell number during embryogenesis and blastogenesis of plants
and animals. Mitosis is related with the growth of an individual from zygote to
adult stage. Mitosis starts at the culmination point of interphase (i.e., G2 phase).
It is a short period of chromosome condensation, segregation and cytoplasmic
division.

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Figure 8.1. The cell cyle. The generation time varies widely with the cell type and
species. Most cells spend about 90% of their cell cycle in interphase.

Figure 8.2. Diagrammatic summary of mitosis in higher plant cells.

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 Figure 8.3. Diagrammatic summary of mitosis in the animal cell.
The process of mitosis is similar in all animals and plants. It is divided into four stages
phases (Fig. 8.2 and Fig. 8.3).

8.2.2.1. Prophase.
The appearance of thin thread-like condensed chromosomes marks the first phase of
mitosis, called prohase (Greek, pro=before; phasis=appearance). The cell becomes
spheroid, more refractile and viscous.

Each prophase chromosome is composed of two coiled filaments, the chromatids,

which are the result of the replication of DNA during the S phase. As prophase
progresses, the chromatids become shorter and thicker and two sister chromatids of
each chromosome are held by a special DNA-containing region, called the

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centromere. During prohase, proteins of the trilaminar kinetochores (one for each
chromatid) start depositing or organizing on the centromere of each chromosome.
Further, during early prohase the chromosomes are evenly distibuted in the nuclear
cavity; as prophase progresses, the chromosomes approach the nuclear envelope,
causing central space of the nucleus to become empty.

In the cytoplasm, the most conspicuous change is the formation of the spindle or
mitotic apparatus. In the early prophase, there are two pairs of centrioles, each one
surrounded by the so called aster which is composed of microtubules radiating in all
directions (Figure 8.3). The two pairs of centrioles migrate to opposite poles of the cell
along with asters and become situated in antipodal positions. Between the separating
centrioles forms the spindle (Figure 8.3). The microtubules of the spindle are arranged
like two cones base to base, broad at the centre or equator of the cell and narrowing to
a point at either end or pole. The mitotic spindle contains three types of fibres:
1. polar fibres, which extend from the two poles of the spindle toward the
equator;
2. kinetochore fibres, which attach to the kinetochores of centromeres of each
mitotic chromosome and extend towards the poles;
3. astral fibres, which radiate outward from poles towards the periphery or cortex
of the cell. In higher plants, however, spindle forms withouut the aid of
centrioles and lacks asters (Figures 8.4 and 8.5).

Figure 8.4. mitotic metaphase spindle structure in (A) a plant cell and (B) an animal
cell. Higher plants lack centrioles and astral fibres.

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Figure 8.5. Mitosis in a cell of the endosperm (a food storgae organ in the seed).

During interphase, the nucleolus gradually disintegrates. Degeneration and

disappearance of the nuclear envelope marks the end of prophase. Two factors may be
involved in this process:
1. Enzymatic action either by some mitochondrial enzymes, cytosolic MPF kinase or
nuclear RNA (or ribozyme);
2. Physical action, i.e., physical stress exerted by microtubules which become
attached to the nuclear envelope.

8.2.2.2. Prometaphase.
The breakdown of the nuclear envelope signals the commencement of prometaphase
and enables mitotic spindle to interact with chromosomes. During this stage the
spindle fibres appear to be trying to contain and align the chromosomes at the
metaphase plate (Figure 8.6). At this stage the chromosomes are violently roatated and

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oscillated back and forth between the spindle poles because their kinetochores are
capturing the plus ends of microtubules growing from one or the other spindle pole and
are being pulled by the captured microtubules. Sister chromatids become attached by
their kinetochores to opposite poles; balanced bipolar forces hold chromosomes on the
metaphase plate.

Figure 8.6. The mitotic spindle at metaphase. The spindle is constructed from two half
spindles, each composed of kinetochore, polar and astrial microtubules. The polarity of
microtubules is indicated by the arrowheads.

8.2.2.3. Metaphase.
During metaphase (Greek, meta=after; phasis=appearance) the chromosomes are
shortest and thickest. Their centromeres occupy the plane of the equator of the mitotic
apparatus (a region known as the equatorial or metaphase plate), although the
chromosomal arms may extend in any direction. At this stage the sister chromatids are
still held together by centromere and kinetochores of the two sister chromatids face
opposite poles; this would permit proper seperation in the next phase (anaphase).

Metaphase occupies a substantial portion of the mitotic phase, as if the cell pauses
untill all the chromosomes are lined up appropriately on the metaphase plate. At
metaphase subunits (tubulin dimers) are added to the plus end of a microtubule at the
kinetochore and are removed from the minus end at the spindle pole (Figur 8.6).

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8.2.2.4. Anaphase.
The anaphase (Greek, ana=up; phasis=appearance) begins abruptly with the
synchronous splitting of each chromosome into its sister chromatids, called daughter
chromosomes, each with one kinetochore. Anaphase involves the following two steps:
(i) Anaphase A. During this, there is poleward movement of chromatids due
to shortening of kinetochore microtubules. During their poleward
migration the centromeres (and kinetochores) remain foremost so that
characteristically appear U, V or J-shaped (Figures 8.2 and 8.3).
(ii) Anaphase B. It involves seperation of poles themselves accompanied by
the elongation of the polar microtubules. The astral microtubules also help
in anaphase B by their attraction with the cell cortex.

8.2.2.5.Telophase.
The end of the polar migration of the daughter chromosomes marks the beginning of
the telophase; which in turn is terminated by the reorganization of two new nuclei and
their entry into the G1 phase. In general terms, the events of prohase occur in reverse
sequence during this phase:
 a nuclear envelope reassembles around each group of chromosomes to
form two daughter nuclei;
 the mitotic apparatus except the the centrioles disappears;
 high viscosity of the cytoplasm decreases;
 the chromosomes resume their long, slender, extended form as their
coils relax;
 and RNA-synthesis restarts causing the nucleolus to reappear.

8.2.2.6. Cytokinesis
Both DNA synthesis and mitosis are coupled to cytoplasmic division, or cytokinesis-
the constriction of cytoplasm into two seperate cells. During cytokinesis, the
cytoplasm divides by a process called cleavage. Cytokinesis usually begins in
anaphase and continues through telophase into interphase. The first sign of cleavage
in animal cells is puckering and furrowing of the plasma membrane during anaphase.
Cleavage is accomplished by the contraction of a ring composed mainly of actin
filaments (Figure 8.7).

Figure 8.7. Cytokinesis in an animal cell.

In animals, the cell separates into two through a pinched area known as the cleavage
furrow while in plants the cells separates into two by the cell plate. At the end of

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mitosis two daughter cells are produced and each of them contains the same number of
chromosomes as the mother cell.

8.2.3 Significance of mitosis

Mitosis is important for:
 replacement of cells lost to natural friction (attrition), wear and tear,
 wound healing,
 asexual reproduction e.g budding in yeast and hydra and vegetative
propagation in plant,
 maintaining proper cell size,
 maintaining the amount of DNA and RNA in the cell,
 providing opportunity for growth and development to organs and the
body of the organisms,
 increasing the number of sex cells,
 cleavage of egg during embryogenesis and division of blastema during
blastogenesis.
8.3 MEOSIS

Meiosis (Greek, meioum=to reduce or to diminish) produces a total of four haploid

cells from each original diploid cell. The haploid cells either become or give rise to
gametes, which through union (fertilization) support sexual reproduction and a new
generation of diploid cells.Thus, meiosis is required to run the reproductive cycle of
eukaryotes.

8.3.1 Process of Meiosis

Meiosis ensures that the number of chromosomes is reduced by half during gamete
formation in order to maintain the chromosome number of the species after
fertilization. Meiosis occurs only in the specialized cells (germ line) of the
reproductive organs (gonads). The testis are the male gonads and ovaries are the
female gonads. Meiosis superficially resembles two mitotic divisions without an
intervening period of DNA replication. The first meiotic (meiosis I) division includes a
long prophase in which the homologous chromosomes become closely associated to
each other and interchange of hereditory material takes place between them. Further, in
the first meiotic division the reduction of chromosome number number takes place
and, thus, two haploid (n) cells are resulted by this division. In the second meiotic
(meiosis II) division the haploid cell divides mitotically and results into four haploid
(n) cells.

Unlike mitosis the end products (gametes) of meiosis must first undergo fertilization to
produce a zygote which develops into an individual organism. The produced individual
will then produce gametes which will also undergo fertilization (Figure 8.8).

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Figure 8.8. Life cycle of higher animal (human being).

8.3.2 First Meiotic Division (Meiosis I)

Meiosis starts after an interphase which is not very different from that of an
intermitotic interphase. Meiosis I is a reduction divion that produces two haploid cells
from a single diploid cell. It consists of four major phases (i) prophase I, (ii) metaphase
I, (iii) anaphase I and (iv) telophase I (Figures 8.9 and 8.10)

8.3.2.1. Prophase I.

During prophase I homologous chromosomes come to lie side by side in a pairing

process called synapsis producing a pair of chromosomes called a bivalent. Each
chromosome consists of two identical sister chromatids. A bivalent may also be called
a tetrad (4 chromatids). Synapsis occurs when non-sister chromatids (one from each of
the paired chromosomes) of a tetrad cross over and exchange chromatin material. The
crossing over is accompanied by formation of a chiasma (plural = chiasmata). Only
two of the four chromatids cross over (in a random manner) at each chiasma.
Generally, longer chromosomes will have a higher number of crossovers.

8.3.2.2 Prometaphase
In the prometaphase, the nuclear envelope disintegrates and the microtubules get
arranged in the form of spindle in between the two centrioles which occupy the
position of two opposite poles of the cell. The chromosomes become greatly coiled in
the spiral manner and get arranged on the equator of the spindle.

8.3.2.3. Metaphase I
During metaphase I, the bivalents align themselves at random on the equatorial plane.
This random orientation promotes independent assortment of the chromosomes and
their genes. The microtubules of the spindle are attached with centromeres of the
homologous chromosomes of each tetrad. The centromere of each chromosome is
directed towards the opposite poles. The repulsive forces between the homologous
chromosomes increase greatly and the chromosomes become ready to separate.

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8.3.2.4. Anaphase I
During anaphase I, the centromeres do not divide, but continue to hold sister
chromatids together. Because during the chiasma formation out of two chromatids of a
chromosome, one has changed its counterpart, therefore, the two chromatids of a
chromosome do not resemble with each other in the genetic terms (Figure 8.10).
Homologous chromosomes (each consisting of 2 sister chromatids) separate and move
to opposite poles. This movement reduces the chromosome number from the diploid
(2n) condition to the haploid (n) condition.

8.3.2.5 Telophase I
The first meiotic division effectively ends when the chromosomes arrive at the poles.
Each daughter cell now has half the number of chromosomes but each chromosome
consists of a pair of chromatids. The nuclear membrane reappears and surrounds the
haploid set of chromosomes. The chromosomes uncoil back into chromatin.
Cytokinesis in telophase I divides the diploid mother cell into 2 haploid daughter cells.
This involves the formation of a cleavage furrow in animal cells or the formation of
the cell plate in plant cells, occurs (Figure 8.10). Sister chromatids remain attached
during telophase I.

8.3.3 Interkinesis
The period between the first and second meiotic divisions is called interkinesis or
interphase II. The DNA does not replicate during interkinesis.

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Figure 8.9. The stages of meiosis in an animal cell.

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Figure 8.10. Diagrammatic representation of meiosis in a plant cell showing one pair
of homologous chromosomes.

8.3.4. Meiosis II
The second meiotic division (meiosis II) is an equational division (mitosis-like), in
which sister chromatids of the haploid cells are separated. This process is similar to
mitosis, though the cells produced have half the number of chromosomes. Meiosis II
also consists of four major phases (prophase II. metaphase II, anaphase II, and
telophase II).

8.3.4.1. Prophase II
In prophase II, the nuclear membrane disappears and the spindle fibres reappear. The
chromosomes with two chromatids become short and thick in readiness for the second
meiotic division (Figure 8.9).

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8.3.4.2 Metaphase II
At metaphase II, the individual chromosomes line up on the equatorial plane. The new
equatorial metaphase plate is rotated by 90 degrees compared to meiosis I plate and is
therefore perpendicular to the metaphase I plate. The centromere divides into two and,
thus, each chromosome produces two daughter chromosomes. The microtubules of the
spindle are attached with the centromere of the chromosomes.

8.3.4.3 Anaphase II
During anaphase II, the centromeres of each chromosome divide, allowing the sister
chromatids to be pulled apart in an equal division (mitosis-like) by the spindle fibres.
The sister chromatids which are now called chromosomes move toward opposing
poles due to the shortening of chromosomal microtubules and stretching of interzonal
microtubules of the spindle.

8.3.4.4. Telophase II
During telophase II, which is similar to telophase I, the chromosomes uncoil and
lengthen. The spindle fibres disappear and the nuclear membrane reforms and there is
formation of either a cleavage furrow (in animal cells) or cell plate (in plants)
producing a total of four daughter cells, each with a haploid set (half the number) of
chromosomes. The cells have different types of chromosomes due to the crossing over
in the prophase I.

8.3.5. Significance of Meiosis

1. Meiosis maintains a definite and constant number of the chromosomes in the
organisms.
2. By crossing over, the meiosis provides an opportunity for the exchange of
the genes and, thus, causes the genetic variations among the species. The
variations are the raw materials of the evolutionary process.

8.4. Revision questions

1. What is cell division?

2. How many types of cell divisions occur in eukaryotic organisms?
3. Discuss the use and biological significance of each type of cell division.
4. Define the terms: cell cycle and mitosis.
5. Name stages of the cell cycle.
6. Which phase is usually the longest phase?
7. What are the major features of each mitotic phase?
8. What basic activities occur during mitosis?
9. How does mitosis differ in animal and plant cells?
10. What biochemical events occur in cells before visible cellular division occurs?
11. Describe the behaviour and presumed role of centrioles during mitosis.
12. What is meiosis?
13. Describe the major features of each miotic phase.
14. Discuss the significance of meiosis during gamete production.
15. Summarise the events of the first meiotic prophase.
16. Which phases of meiosis are the same as the corresponding mitotic phase and
which are different? In what ways do they differ?

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 17. Describe the various roles of cytoskeleton during mitosis; stress on the function
of mitotic spindle during anaphase A and anaphase B.
18. Describe the role of microtubules in chromosome movement during mitosis
and meiosis.
19. What is cytokinesis?
20. Describe the process of cytokinesis in animal and plant cells.
21. What is a division furrow and contractile ring?
22. Write short notes on the following: (i) G0 phase (ii) Cell cycle (iii) Mitotic
spindle.

Table 8.1

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