The cell cycle: What do you need to know about it Paul R' Earl Facultad de Ciencias Biolgicas Univer

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The cell cycle What do you need to know about it
?Paul R. EarlFacultad de Ciencias
BiológicasUniversidad Autónoma de Nuevo LeónSan
Nicolás, NL, Mexico
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Cytology is simply any study of the cell,
although by a long tradition, study by the light
microscope is implied. Cytology is often
connected with genetics to become cytogenetics as
developed over a century ago in Europe, and then
mainly by the Thomas Hunt Morgan (1866-1945)
school of Columbia University in New York with
Calvin Bridges (1889-1938) and Alfred Sturtevant
(1891-1970), and also Hermann Muller (1890-1967).
In 1902 1903, Walter Sutton (1877-1916) and
Theodor Boveri (1862-1915) had refined gametic
meiosis that explains Mendelism.
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Boveri had named the centromere in 1901.
In 1914, Boveri proposed his supertheory that
aneuplody causes cancer. In 1910-1913, Morgan and
Bridges established that the genes were in the
chromosomes, and Sturtevant who wrote The History
of Genetics (1965) found that the genes were
arranged in a line. Imagine the problem if they
were not ! By 1927, Hermann Muller (1890-1967) of
the Columbia group found that X-rays caused
chromosome breaks and increased the mutation
rate. Another powerful contributor to cytology
was Cyril Darlington (1903-1981) on gametic
meiosis.
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Cytogenetics is chiefly the visible knowlege
obtained with various kinds of microscopes.
Genetics is the body of inferred knowledge
obtained by all means of study, including, for
instance, PCR. See Blystone R. 2003. WWW.Cell
Biology Education. Cell Biol Ed 2 214219, also
vysa.com and cytocell.co.uk, and
www.molbiolcell.org/cgi/doi/10.1091/
mbc.E03110794.
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Meiosis contains a reduction division. When the
chromosomes are halved before mating which likely
involves crossingover, haploid (single set)
gametes are formed. This is 1 1 2 as 23
haploid plus 23 haploid the 46 diploid set of
chromosomes in humans. Twenty-two pairs are
autosomes, whereas X Y are female (XX) and male
(YX) sex chromosomes, verified long ago by
Stevens.When the number of chromosomes is
doubled to form a karyosome (synkaryon) or
fertilization nucleus, then reduced immediately
or in the 2nd division, this is zygotic or
haploid meiosis as 1 1 2, then 2 -1 1.
Zygotic meiosis occurs in some protozoans, fungi
and yeasts. Then the soma of algae like Spirogyra
is haploid. Meiosis reduction is AFTER not
before fertilization.
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In the 1st meiotic division--reduction--2
successive rounds of chromosome segregation
follow a single round of DNA duplication,
producing 4 haploid products. The segregation of
homologous pairs of chromosomes at the 1st
division is dependent on their previous pairing,
synapsis and recombination from crossingover at
earlier stages.The 2nd meiotic division serves
to separate the 2 sister chromatids of each
chromosome. Subsequent fertilization of male and
female gametes restores the diploid state.
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Mitosis in salamander skin as illustrated here
was drawn by Flemming in 1882. In a-c
prophase chromosomes are condensing and later
aligning to move towards the metaphase plate (i).
Metaphase, d-f, contains 2 sets of chromosomes
that separate during anaphase, g-h. In telophase
is i-j or even g-j, if you like. Karl von Nägeli
(1817-1891) noted chromosomes in 1842 so named in
1888 by Heinrich WG Waldeyer-Hartz
(1836-1921).
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The entire cytological advance depended on
selective dyes that were developed by the German
chemical industry in the 19th century.During
meiosis, homologous maternal and paternal
chromosomes become linked by cytologically
observable connections that are chiasmata (breaks
and bridges). Each chiasma is the site of a DNA
crossover between one sister of each homolog.
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The Hayflick limitLong ago and far away, the
Algerian librarian Emile Maupas (1844-1916) in
1889 found that clones of the ciliate Paramecium
eventually died out, yet he also discovered that
these ciliates were rejuvenated if fertilized.By
1959 at the Wistar Institute in Philadelphia,
published in 1965, Lennie Hayflick found that
normal human diploid primary cell lines would
only grow in tissue culture for some 50 plus
generations. He was looking for a cheaper way to
grow polio virus than in primary rhesus kidney
cells. They, like all normal cells, died out
after a very few months.
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MitosisThe cell cycle has 2 phases interphase
and mitosis. Interphase consists of G1, S and G2
phases. Growth 1 2, and DNA Synthesis.Mitosis
can be subdivided into 1/ prophase, 2/
metaphase, 3/ anaphase and 4/ telophase.
Chromosomes condense during prophase, align
during metaphase, separate during anaphase and
decondense during telophase. There are several
control checkpoints during the cell cycle. One in
late G1 is Start in yeast called the Restriction
point in mammals. It is active in late G2 and
just before anaphase.
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• PROPHASEThe 2 centrosomes of the cell, each
  with its pair of centrioles, move to opposite
  poles of the cell.
• The spindle polar body forms an array of about
  20 spindle fibers each, growing out from each
  centrosome. Chromosomes condense to become
  shorter and more compact.

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CYTOKINESIS is cytoplasmic division as
karyokinesis is nuclear movement that is equal to
nuclear division.A typical centrosome is about 1
µm3 in volume and composed of a pair of
centrioles surrounded by a matrix of
pericentriolar material. The centrioles consist
of a cylinder formed by microtubules arranged
with perfect nine-fold symmetry. The
pericentriolar matrix contains several large
coiled-coil proteins and the tubulin ring
complex. The centrosome does not have a
membrane.
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Animal cells have one centrosome in G1 phase of
the cell cycle that duplicates once in the S
phase to form a bipolar spindle during mitosis.
The duplication of centrioles is
semiconservative--one old, one new. The 2
original centrioles separate and a new centriole
grows adjacent to each to form 2 complete
centrosomes. Tubulin subunits as in the
centrioles are in abundance.In animal cells, a
belt of actin filaments forms around the
perimeter of the cell midway between the poles.
The interaction of actin and a myosin (not the
one found in skeletal muscle!) tightens the belt,
pinching it into 2 daughter cells.
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CheckpointsWe mentioned Start. To pass each
point, cells have to fulfil several
prerequisites. Before passing Start, cells can
undergo 2 developmental programs, vegetative
reproduction--mitosis or sexual
development--meiosis.A cell must replicate all
of its components and divide them into 2 nearly
identical daughter cells. As DNA stores the
genetic information, it must be accurately
replicated in the S phase of the cycle. DNA
duplication results in 2 identical sister
chromatids, which must be precisely segregated.
Segregation of sister-chromatids happens during
mitosis (the M phase).
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G0 is interphase lasting for days at least.
Also, adequate nutritional conditions and a
critical cell size are required to engage Start.
During G2, cells have to check whether DNA
replication is completed and ensure that DNA is
undamaged. Before chromosome separation, cells
check whether the chromosomes are aligned and
spindle polar body are formed properly.
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MeiosisIn gametic meiosis I division (MI), the
homologous chromosomes separate, but the sister
chromatids remain attached, thus going to the
same pole. This is the reductional division,
because it essentially reduces the ratio of
chromosomes in the daughter nuclei from 2 to 1.
In zygotic meiosis, the karyosome in 1 or 2 steps
will segregate the zygote into 2 haploid sets.
You must be very clear about the natural
consequences of the reduction, and, in yeast,
possibly look for controls for meiosis.
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A
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B
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Three irreversible transitions are present in
the mitotic cycle 1/ Start, when the cell
commits itself to cell division, 2/ G2/M
Transition, when the cell commits itself to enter
into mitosis, and 3/ Finish, when the cell exits
from mitosis (ana- phase, telophase, cell
division).Cells are driven through the cell
cycle by an underlying molecular engine of
protein molecules.
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In higher eukaryotes, many Cdkcyclin complexes
trigger different cell-cycle events. In lower
eukaryotes, like fission yeast, a single
Cdkcyclin complexcan drive the whole cell
cycle. This complex is called Cdc2Cdc13 in
fission yeast Cdc2 is the Cdk subunit and Cdc13
is the major B-type cyclin in fission yeast
cells.Cdc2 is present at a constant level
throughout the cell cycle, and it is in excess
over Cdc13. Cdc13 is continuously synthesized and
it combines with Cdc2 to form an active
Cdkcyclin complex. Study the diagram by Novak
and Tyson.
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By now, we have covered What You Need to Know
about the Cell Cycle.Two special topics are now
noted Pap smears (George Papanicolaou,
1883-1962) and Fluorescence in situ hybridization
(FISH). In addition, a Glossary is added and a
list of over 200 References.