cell

Eukaryotes (meaning true nucleus) are organisms

with cells within which the genetic material (DNA) is

located in the nucleus (a discrete structure bounded

by a nuclear envelope).

In contrast to eukaryotes, prokaryotes (meaning

prenuclear) do not have a nucleare envelope

surrounding their DNA.

Ploidy and the cell cycle

The number of different chromosomes in any nucleated cell, the

chromosome set, and the associated DNA content are designated n and

C respectively.

For human, n=23 and C=approximately 3.5pg.

Sperm and egg cells carry a single chromosome set and are said to be

haploid (n chromosomes and DNA content=C).

Most human cells, however, carry two copies of the chromosome set

and are diploid (2n chromosomes and DNA content=2C).

Tetraploid (4n), polyploid (>4n) as a result ofDNA replication without cell

devision (endomitosis) or as a result of cell fusion the ploidy of hepatocytes

ranges from 2n to 8n or cardiomyocytes from 4n to 8n or giant

megakaryocytes of the bone marrow from 16n to 64n which give rise to

thousands of nulliploid platelet cells, triploidy (3n)=less common because

triploids have problems with meiosis.

Nulliploid in some terminally differentiated cells, such as red blood cells,

keratinocytes and platelets.

Chromosome

The chromosomes are distinguishable on the basis of their size,

centromere position, and banding pattern.

The centromere may be in the middle, off-center, or close to one

end- metacentric (1,3,19,20), submetacentric, and acrocentric,

respectively.

Acrocentric chromosomes have one arm with a stalk and often

with a ‘’bulb’’ (called a satellite) on it ; 13,14,15,21,22 (repeated

bp of rRNA genes).

Telocentric chromosomes have only one arm, because the

centromere is at the end.

Originally the chromosomes were assigned to groups A through G

according to their general size and the position of the centromere.

With banding, each chromosome is individually distinguishable.

The diagrammatic representation of the banding pattern is the idiogram.

chromosome

Chromosomes have a linear appearance: two arms are

continuous at the centromere.

The shorter arm is designated p (for petit, french) and the longer

is q (next letter in the alphabet).

In the early part of the cell cycle, each chromosome is present

as a single structure, a chromatid, a single DNA molecule.

During the cell cycle the chromosomes replicate, and two sister

chromatids form.

The autosomes are numbered from largest to smallest, no.1 through 22

(to split hairs, this order is not exact: for example, chromosome 10 and 11

are shorter than chromosome 12, and chromosome 21 is smaller than 22).

The 46 chromosomes come in 23 matching pairs, and constitute the

genome.

MitosisThe M phase of the cell cycle consists of the various stages of nuclear

division; prophase, prometaphase, metaphase, anaphase and

telophase of mitosis, and cell division (cytokinesis) which overlaps the

final stages of mitosis.

The chromosomes contract during late prophase to become thicker

and shorter (chromosomal condensation).

During late prophase of mitosis, a pair of large multiprotein complexes

known as kinetochores, forms at each centromere, one attached to

each sister chromatid. Microtubules attach to each kinetochore, linking

the centromere of a chromosome and the two spindle poles.

At anaphase, the kinetochore microtubules pull the two sister chromatids

toward opposite poles of the spindle.

Kinetochores play a central role in this process, by controlling assembly

and disassembly of the attached microtubules.

MitosisIn late prophase, the nuclear membrane disappears and metaphase

begins.

At this point, the mitotic spindle becomes visible as thin threads. It

begins at two polelike structures (centrioles).

The interaction between the different spindle fibres pulls the

chromosomes toward the center, and by metaphase each chromosome

is aligned on the equatorial plane (metaphase plate).

During mitosis each chromosome in the diploid set behaves

independently and paternal and maternal homologs do not associate at

all.

At anaphase the centromeres divide leading to physical separation of

what were previously sister chromatids, and the pull by the spindle fibers

ensure that the separated sister chromatids go to oppsite poles.

The DNA of the two sister chromatids is identical, barring any errors in

DNA replication.

The stages of MitosisProphase: the chromatides are very elongated and they begin to coil

tightly.

So they appear shorter and fatter under the microscope.

Metaphase: the nuclear envelope has completely disappeared.

The microtubules attached to the kinetochores orient the chromosomes

so that their centromeres become aligned in one plane halfway between

the two spindle poles.

Anaphase: It begins when the joined centromeres of sister chromatids

separate, giving rise to two daughter chromosomes.

Telophase: During this stage the migration of daughter chromosomes to

the two poles is completed.

Result of Mitosis

Thus the effect of mitosis is to generate daughter

cells that contain precisely the same set of DNA

sequences.

Interphase and the stages of mitosis in whitefish early embryo cells

Meiosis

Meiosis is the two successive division of a diploid nucleus after only

one DNA replication (chromosome duplication) cycle.

Primordial germ cells migrate into the embryonic gonad and engage in

repeated rounds of mitosis to form oogonia in females and

spermatogonia in males (this involves many more mitosis in males than

females which may be a significant factor in explaining sex differences

in mutation rate).

Further growth and differentiation produces primary oocytes in the

ovary and primary spermatocytes in the testis.

In males, meiosis’ product is four spermatozoa; in females, however,

there is asymmetric cell division because the cytoplasm divides unequally at

each stage: the products of meiosis I (the first meiotic division) are a large

secondary oocyte and a small cell (polar body).

During meiosis II (the second meiotic division) the secondary oocyte then

give rise to the large mature egg cell and a second polar body.

Meiosis’ stages 1Meiosis I: Prophase I;

1. Leptonema (early prophase I, the leptotene stage): the extended

chromosomes begin to coil and become visible as long, thin threads.

2. Zygonema (early to midprophase I, the zygotene stage): the

chromosomes continue to shorten.

The homologous pairs of chromosomes actively find each other and

align roughly along their length.

Each pair of homologs then undergoes synapsis –the formation along

the length of chromatids of a zipperlike structure called the

synaptonemal complex, which aligns the two homologs precisely; base

pair for base pair.

The telomeres of chromosomes play an important role in the initiation

of synapsis.

They clustered on the nuclear envelope to produce an arrangement

called a bouquet, because of its resemblance to the stems from a

bouquet of cut flowers.

In some way, the telomeres move the chromosomes around so that

homologous chromosomes align and undergo synapsis.

Meiosis’ stages 23. Pachynema: (midprophase I, the pachytene stage);starts when

synapsis is completed and each synapsed set of homologous

chromosomes consists of 4 chromatids which called a bivalent or a

tetrad.

Crossing-over is a significant event for genetic which the reciprocal

physical exchange of chromosome segments at corresponding

positions along pairs of homologous chromosomes occurs.

This exchange 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 (The new

chromosomes called recombinant chromosome).

Meiosis’ stages 34. Diplonema: (mid-to late prophase I, the diplotene stage): 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).

Even though the sex chromosomes are not homologous, the Y

chromosome of eutherian (placental) mammals has small regions at

each end that are homologous to regions on the X chromosome.

These pseudoautosomal regions (PARs) pair in male meiosis, and

crossing-over occurs between them.

When the PAR is deleted from the short arm of the Y chromosome,

pairing between the X and Y chromosomes does not occur, and male

is sterile.

• In most organisms, diplonema is followed rapidly by the remaining

stages of meiosis, However, in many animals, the oocytes (egg cells)

can remain in diplonema for very long periods.

• In human females, for example, oocytes go through meiosis I up to

diplonemaby the seventh month of fetal development and then remain

arrested in this stage for many years.

• At the onset of puberty and until menopause, one oocyte per

menstrual cycle completes meiosis I and is ovulated.

5. Diakinesis (late prophase), the nucleoulus and nuclear envelope

break down. Simultaneously, the spindle is assembled.

• The chromosomes can be counted most easily at this stage of

meiosis.

Meiosis’ stages 4Metaphase I: The nuclear envelope has completely broken down and

the bivalents become aligned on the equatorial plane of the cell.

• The spindle is completely form now, and the microtubules are attached

to the kinetochores of the homologs.

Anaphase I: The chromosomes in each bivalent separate, so the

chromosomes of each pair disjoin and migrate toward opposite poles (in

this stage, each of separated chromosomes called a dyad).

Telophase I: The dyads complete their migration to opposite poles of the

cell, and (in most cases) new nuclear envelopes form around each

grouping.

Meiosis’ stages 5

Meiosis II: The second meiotic division is similar to a meiotic

division.

1. Prophase II: The chromosomes condense.

2. Metaphase II: Each of the two daughter cells organizes a spindle

apparatus which attaches to the centromeres that still connect the

sister chromatids.

• The centromers line up on the equator of the second-division

spindles.

1. Anaphase II: The centromeres split, and the chromatids 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.

1. Telophase II: A nuclear envelope forms around each set of

chromosomes, and cytokinesis takes place.

Gene segregation in MeiosisMeiosis has three significant results:

1. Meiosis generates haploid cells which fusion of haploid nuclei

restores the diploid number.

2. In metaphase I, each maternally derived chromosome and each

paternally derived chromosome has an equal chance of aligning on

one or the other side of the equatorial metaphase plate.

• The number of possible chromosome arrangements at the metaphase

plate in meiosis is 2 which is more than 4 million combination for

human.

n-1

Meiosis results

3. The crossing-over between maternal and paternal chromatid

pairs during meiosis I generates still more variation in the final

combinations.

Mitosis and meiosis differences

There are two crucial differences between mitosis and meiosis

1. The products of mitosis are diploid; the products of meiosis are

haploid.

2. The products of mitosis are genetically identical; the products of

meiosis are genetically different.

• Another key difference between mitosis and meiosis I is that

sister chromatids remain joined after metaphase in meiosis I,

whereas they separated in mitosis.

Roberts syndrome

Autosomal recessive disorder characterised by: craniofacial anomalies,

limb reduction defects and loss of cohesion at heterochromatin regions

of centromeres (chromosome puffing)

Cancer is a disease of the cell cycle

Cells grow in vitro undergo a characteristic number of divisions.

• Once this number, known as the Hayflick limit, is reached, the cells stop

dividing.

• Cells from human embryos have a limit of about 50 divisions.

• Cells from adults can divide only about 10 to 30 times.

Several genetic disorders that affect cell division are associated with

accelerated aging (Progeria).

Hutchinson-Gilford Progeria syndrome

The word progeria is derived from the Greek for "prematurely old".

The condition is distinguished by limited growth, alopecia and a

characteristic appearance with small face and jaw and pinched nose.

Later the condition causes wrinkled skin, atherosclerosis and

cardiovascular problems.

Mental development is not affected. Individuals with the condition rarely

live more than 16 years; the longest recorded life-span was 29 years.

The development of symptoms is comparable to aging at a rate six to

eight times faster than normal, although certain age-related conditions

do not occur.

Specifically, victims show no neurodegeneration or cancer

predisposition.

Cancer is a disease of the cell cycle

Werner Syndrome is an other genetic disorder associated with

premature aging.

In this case, the disease process begins between the ages of 15 and 20

years, and affected individuals die of age-related problems by 45 t0 50

years.

It is characterised by: premature greying an thinning of the hair, short

stature, prematurely aged appearance, osteoporosis, diabetes mellitus

type 2, hypogonadism, premature atherosclerosis, a weak or hoarse

voice, and cataracts.

Questions

A cell from a human female has just undergone mitosis. For unknown reasons, the centromere of chromosome 7 failed to divide. Describe the chromosomal contents of the daughter cells?

How can errors in the cell cycle lead to cancer in humans?

Mitosis and Meiosis always differ in regard to the presence of:

1. Chromatids

2. Homologs

3. Bivalents

4. Centromeres

5. spindles