Chapter 12 THE CELL CYCLE

The continuity of life is based on the reproduction of cells, or cell division.

Rudolph Virchow observed cells dividing and giving rise to new cells in 1855.
Cell division is involved in reproduction, growth and repair.
CELL DIVISION RESULTS IN IDENTICAL DAUGHTER CELLS
The whole of genetic inforation in a cell is called the genome, the organis!s genetic aterial.
The pro"aryote genoe consists of a single #$% olecule& the eu"aryote genoe is ade of
several #$% olecules.
#$% is pac"aged into chromosomes.
Chroosoes get their nae fro the 'ree" words chroma, color and soma, body.
Chromatin is ade of #$% and associated proteins.
% chroosoe is ade of highly coiled and condensed chroatin.
(n non)dividing cells, the chroatin is e*tended and uncoiled.
Chroosoes are or organi+ed into inforational units called genes.
,very individual of a species has the characteristic nuber of chroosoes of the species, e.g.
all huans have -. chroosoes in their soatic or body cells and 2/ in the reproductive cells
or gaetes.
The nuber varies fro species to species.
(t is possible for an individual to have an abnoral nuber of chroosoes.
The inforation in the chroosoes is what a"es the uni0ueness of the species and not the
nuber of chroosoes.
Chroosoes e*ist in pairs, half of which was been contributed by each parent of the
individual.
1ody cells have the full copleent of chroosoes and they are called di!oid cells.
'aetes have only half of the species chroosoes and they are called ha!oid.
DISTRI"UTION O# CHRO$OSO$ES DURING CELL DIVISION
#$% has the ability to replicate. % replicated chroosoe has two sister chromatids with a
narrow region called the centromere.
Cell division involves two processes,
1. $itosis2 it involves the nucleus and it insures that each daughter cell will receive the
sae nuber and type of chroosoe as were present in the original nucleus.
2. C%to&inesis2 refers to the division of the cytoplas of the cell to for two daughter cells.
3hen itosis is not followed by cyto"inesis, the cell becoes m'!tin'c!eated or coenoc%tic.
Reproductive cells norally have half of the nuber of chroosoes of the parent cell. This
process of cell division that reduces the nuber of chroosoes in half is called meiosis.
4eiosis occurs only in the gonads2 ovaries and testes.
THE $ITOTIC CELL CYCLE
The 'eran anatoist 3alther 5leing developed dyes in 1882 that allowed hi to observe
the behavior of chroosoes during itosis and cyto"inesis.
6e coined the naes mitosis and chromatin.
The cell cycle is the period of tie fro the beginning of one cell division to the beginning of the
ne*t division.
The tie it ta"es for the cycle to be copleted is called the generation time.
'eneration tie can vary widely.
The itotic phase includes itosis and cyto"inesis, is the shortest part of the cycle. The
interphase is uch longer and often accounts for 789 of the cycle.
A( Interhase.
4any critical events ta"e place during the interphase.
(n the interphase, the cell replicates the chroosoes and grows.
(t can be divided into the )irst ga hase *G+,, chromosoma! s%nthesis hase *S,, and the
second ga hase *G-,.
#irst ga hase *G+,. the cell grows and prepares itself for the : phase.
Chromosoma! s%nthesis hase *S,. #$% and chroosoal proteins are synthesi+ed.
Second ga hase *G-,2 protein synthesis increases in preparation for cell division.
Cells that are not dividing becoe arrested at the '1 stage, which is not part of the cell cycle.
Cells at this state are called to be at the Go state.
The nucleus and nucleolus ;nucleoli< are well defined.
4itosis is conventionally bro"en down into five stages2 prophase, proetaphase, etaphase,
anaphase, and telophase.
The $itotic Sind!e
The itotic spindle begins to for during the prophase.
The spindle consists of fibers ade of icrotubules and associated proteins.
3hile the spindle assebles, the other icrotubules of the cytos"eleton partially disasseble.
The icrotubules are ade of units of the protein t'/'!in.
The assebly of the icrotubules starts in the centrosomes in anials.
Centrosoes are also called microt'/'!e0organi1ing center or 4T=C.
The anial centrosoes consist of two centrio!es surrounded by the pericentriolar aterial,
>C4, an aorphous i*ture that contains different types of proteins.
>lants lac" centrosoes or have centrosoes without centrioles. >lants have centers of
icrotubule foration scattered throughout the cytoplas.
#uring the interphase, the centrosoe duplicates into two centrosoes with centrioles and
ove apart fro each other during the prophase and proetaphase of itosis.
%s the centrosoes ove to opposite ends of the cells, the icrotubules for the itotic
spindle.
% radial array of icrotubules e*tends fro each centrosoe foring the aster.
The function of the aster is not understood.
Centrosomes and Cancer
Cancer cells often have more than the normal number (1 or 2 depending on the stage of the cell cycle) of
centrosomes . They also are aneuploid (have abnormal numbers of chromosomes), and considering the role
of centrosomes in chromosome movement, it is tempting to think that the two phenomena are related.
utations in the tumor suppressor gene p!" seem to predispose the cell to e#cess replication of the
centrosomes.
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,ach of the two sister chroatids of a chroosoe has a "inetochore, a structure of proteins
associated with specific sections of chroosoal #$% at the centroere.
The two "inetochores face in opposite directions.
#uring proetaphase, soe of the spindle icrotubules attach to the "inetochores.
"( $itosis ensures orderly distribution of chroosoes.
1. 2rohase2 duplicated chroosoes are condensed into two sister chromatids held
together at the centromere3 the nucleolus disappear& nuclear envelope brea"s down&
sind!e of icrotubules begins to for.
#ividing cells have a microt'/'!e4organi1ing center ;4T=C< at each pole, fro which
the icrotubules grow outward.
(n anial cells, the microt'/'!e organi1ing center, 4T=C, has a pair of centrio!es in
its center and which the pericentriolar aterial surrounds.
The spindle icrotubules end in the ericentrio!ar materia!. >rotein fibrils a"e the
pericentriolar aterial.
The 4T=C of higher plants lac" centrioles and is ade of dense fibrillar aterial.
The centrosoes ove away fro each other apparently due to the lengthening of the
icrotubules between the.
2. #uring the rometahase, the nuclear envelope fragents& the icrotubules e*tend into
the nuclear area fro pole to pole where the centrosoes are now located& soe
icrotubules becoe attached to the &inetochore of the centroere.
/. $etahase2 chroosoes align at the cell!s e0uatorial plane& itotic spindle is finished&
"inetochores of sister chroatids are attached to icrotubules to opposite poles of the cell.
The chroosoes gather in an iaginary plane at the e0uator of the cell roughly half
way between the poles of the spindle. This arrangeent of the chroosoes is called
the metahase !ate.
The itotic spindle is ade of two types of icrotubules, the o!ar microt'/'!es that
overlap at the e0uator, and the &inetochore microt'/'!es that are attached at the
"inetochore of the centroere.
4icrotubules fro opposite poles of the cell attach at the "inetochore of one of the two
sister chroatids. The entire arrangeent of icrotubules attached to chroosoes in
the etaphase plate is called the sind!e because of its shape.
-. Anahase2 sister chroatids becoe separated and ove to opposite poles of the cell&
each free chroatid is referred now as a chroosoe.
The overall oveent of chroosoes to their respective poles is poorly understood.
(t sees that t'/'!in 'nits are disassebled at the poles and the icrotubules shorten
pulling the chroosoes.
>olar icrotubules are not connected to "inetochores but are part of the spindle.
%s the polar icrotubules elongate, the poles are pushed farther apart, which also
pushes the chroosoes apart since they are attached to the poles by the "inetochore
icrotubules.
%t the end of the anaphase, each pole has the sae nuber of chroosoes.
5. Te!ohase2 a nuclear envelope re)fors around each set of chroosoes& aterial fro
the endoebrane syste contributes to the foration of the nuclear ebrane& nucleoli
are also fored& spindle disappears& chroosoes uncoil.
C( C%to&inesis norally begins during telophase and overlaps with itosis.
The process is also "nown as c!ea5age.
The appearance of the c!ea5age )'rro6 ar"s the beginning of cyto"inesis.
1. The cytoplas divides to for two individual cells.
2. (n anial cells, @ust inside the plasa ebrane, a ring of icrofilaents contracts,
producing a furrow that divides the cytoplas.
/. The ring is ade of actin icrofilaents associated with yosin olecules.
-. (n plant cells, the cell plate provides aterials for new plasa ebranes and cell walls.
There is no cleavage furrow.
5. The ce!! !ate is fored by the fusion of vesicles that originated in the 'olgi apparatus. The
vesicle ebranes fuse to for the cell plate. The cell plate grows until it fuses with the
plasa ebrane.
.. % new cell wall fors fro the contents of the cell plate.
4ost cytoplasic organelles are distributed randoly to the daughter cells.
4itochondria and chloroplasts have their own #$% and are fored fro the division of
pree*isting organelles usually during the interphase.
"INARY #ISSION IN 2RO7ARYOTES
>ro"aryotes reproduce by a process called /inar% )ission.
4itosis is a nuclear phenoenon and pro"aryotes do not have a nucleus.
1acterial chroosoe consists of a circular #$% olecule and its associated proteins.
1acteria do not produce a spindle or have icrotubules.
The #$% begins to replicate at a specific point on the chroosoe called the origin o)
re!ication.
=nce the #$% of the chroosoe begins to replicate, the origin of replication a"es two copies
that ove toward the opposite poles of the cell.
Replication continues while the origins of replication are at the poles. The cell continues to grow
also until the bacteriu is about twice its original si+e.
=nce replication is finished, the chroosoes separate and ove toward the poles.
The plasa ebrane grows inward and a new cell wall is fored.
EVOLUTION O# $ITOSIS
Two proteins involved in binary fission are related to tubulin and actin strengthening the
hypothesis that evolved fro binary fission.
There are two fors of itosis that ay represent ancient echaniss of cell division.
1. (n dinoflagellates the nucleus reains intact and the chroosoes becoe attached to
the nuclear envelope and separate as the nucleus begins to elongate prior to cell
division.
2. (n diatos, a spindle within the nucleus separates the chroosoes.
REGULATION O# CELL CYCLE
=ne hypothesis states that there are olecular signals in the cytoplas that trigger the ne*t
stage in cell cycle.
% cell cycle control syste of a cyclically operating set of olecules that triggers and
coordinates "ey events in the cell cycle.
%nial cells generally have built)in stop signals that halt the cell cycle at chec&oints until
overridden by go)ahead signals.
The signal reports whether or not the processes have been finished and the cell is ready to
proceed into the ne*t phase.
There are three a@or chec"points where the signal registers their essage. They are at the '1,
'2 and 4 phase.
5or any cells, the '1 chec"point, dubbed the restriction point in aalian cells, sees to be
the ost iportant.
(f a cell receives a go)ahead signal at the '1 chec" point, it will usually coplete the :, '2and 4
phases and divide.
(f the cell does not receive the go)ahead signal, it will enter the 'o and e*it the cycle.
The ce!! c%c!e c!oc&. c%c!ins and c%c!in4deendent &inases
The stages of the cell cycle depend on the fluctuation of activity of two types of protein2 "inases
and cyclins.
Ainases are en+yes that activate or inactivate other proteins by phosphorylating the.
C%c!in4deendent &inases or Cd&s drive the cell cycle and found in an even concentration in
the growing cell.
These Cd"s are in an inactive for until bound to the protein c%c!in, whose concentration
fluctuates cyclically. The activity of the Cd"s rises and falls with the concentration of cyclin.
The cyclin)Cd" cople* is called the mat'ration4romoting )actor or $2#. (t prootes itosis
by phosphorylating other proteins, and initiating the fragentation of the nuclear envelope, the
condensation of the chroatin, and targets various icrotubule)associated proteins involved in
the spindle foration.
1y a feedbac" echanis during the anaphase, 4>5 initiates the destruction of cyclin which
leads to reduction of 4>5 activity. The Cd" coponent in recycled.
$ee fig. 12.1% on page 2"&.
Interna! and e8terna! reg'!ator% c'es
The signaling pathways are only iperfectly "nown.
(nternal cues2 essages fro the "inetochores.
The anaphase does not begin until all the chroosoes are properly attached to the spindle at
the etaphase plate. This ensures that daughter cells do not end up with e*tra or issing
chroosoes.
The signal that delays the anaphase initiates in the "inetochores that are still not attached to the
spindle.
>roteins associated with the "inetochores that are still unattached produce a cheical signal
that "eeps the anahase4romoting com!e8 ;%>C< in an inactive state. This signal stops only
when all the "inetochores are attached to the spindle icrotubules. Then the %>C becoes
active and the cell enters the anaphase.
,*ternal signals2 growth factors.
The presence or absence of certain nutrient proote or inhibit the cell cycle.
Gro6th )actors are proteins released by certain body cells that stiulate other cells to divide.
,.g. platelet)derived growth factor ;>#'5< is ade by the platelets of the blood. (n
their presence other cells called fibroblasts divide& in the absence of >#'A,
fibroblasts do not divide and ultiply. 5ibroblasts have >#'A receptors in their
plasa ebrane that initiates a transduction pathway that activates the
coponents of the cell cycle control syste.
Densit%4deendent inhi/ition occurs when cells reach certain density li"e filling an open
space.
Then the nutrients becoe insufficient and the cells stop dividing until soe cells die
or are reoved, then the cells bordering the gap fill in the space and stop dividing
again.
4ost anial cells e*hibit anchorage deendence.
%nial cells to divide ust be anchored to a substratu. The signals for division
coe fro the plasa ebrane and the cytos"eleton lin"ed to the ebrane.
Cancer
:oe characteristics of cancer cells are2
Cancer cells are not regulated as noral cells and divide out of control foring tuors.
Cancer cells divide constantly and invade other tissues.
The nuclei of cancer cells are enlarged.
:oe cancers have chroosoal utations, either e*tra or issing chroosoes or
parts of chroosoes.
Cancer cells fre0uently have e*tra copies of certain genes, a phenoenon called gene
aplification.
Cancer is also associated with gene utations.
Cancer cells are not speciali+ed.
The spreading of cancer cells fro one tissue to another is called metastasis.
% tuor is a ass of abnoral cells. These cells are abnoral in appearance and function.
$a!ignant t'mors invade other tissues and can etastasi+e transporting cancer cells to other
parts of the body.
Cancer cells do not e8hi/it anchorage or densit% deendent inhi/ition.
3hen noral cells undergo trans)ormation fro noral to cancer cells, the iune syste
recogni+es the and destroys the cancer cells.
(f the cancer cells are not destroyed, a tuor develops which ay be benign if it is contained in
one area or alignant if it invades other organs and interfere with their function.
Cancer cells are abnoral also in other ways2 unusual nuber of chroosoes& their
etabolis becoes abnoral& they ay lose their attachent to other cells of the tissue and
travel through the body
Cellular transforation always involves changes in the genes that influence the cycle control
syste.
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