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Ciclo celular

Mitosis
Meiosis
Apoptosis

Figure 5.32
Copyright 2010 Academic Press Inc.

Crecimiento celular

Duplicar cromosomas

Preparacin para divisin celular

Interfase:
G1-S-G2
Davis P. Clark
Molecular Biology, 2010

Divisin celular

Figure 2.15

M
RER
Davis P. Clark
Molecular Biology, 2010

Copyright 2010 Academic Press Inc.

Ciclo celular
Mitosis o fase M: fase de divisin del ncleo y de
la clula
Fase G1 (Gap 1): ocurren procesos de
transcripcin traduccin y otras actividades
celulares generales
Sntesis o fase S: cuando se replica el genoma
Fase G2 (Gap 2): segundo intervalo de
preparacin y chequeo previo a fase M

Principales
eventos

Molecular Biology of the Gene


Watson et al., 2004
Fifth Edition

Divisin celular mittica


Fase S
Cada duplicado del cromosoma se denomina
cromtida
Las cromtidas de un mismo cromosoma se
denominan cromtidas hermanas
Las cromtidas hermanas se unen mediante una
molcula denominada cohesina

Molecular Biology of the Gene


Watson et al., 2004
Fifth Edition

Molecular Biology of the Gene


Watson et al., 2004
Fifth Edition

Divisin celular mittica


Fase M
Cada par de cromtidas hermanas se une a una
estructura denominada huso mittico
Esta estructura est compuesta por fibras
proteicas largas denominadas microtbulos, los
cuales, se adhieren a uno de los dos centros
organizadores de microtbulos
Centrosomas en clulas animales
Cuerpos polares del huso levaduras y fungis

Divisin celular mittica


Fase M
La adhesin de las cromtidas a los microtbulos
es mediado por el cinetocoro, ensamblado en cada
centrmero
Se disuelve la cohesin entre ambas cromtidas
Luego, se separan las cromtidas hermanas

Divisin celular en organismos


superiores
La fase M para que ocurra debe:
Replicarse el ADN
En clulas animales: replicacin de los
centrosomas, centro organizador de los
microtbulos
Compuesto por dos centriolos
Matriz del centrosoma o material
pericentriolar

Fase S y M del ciclo de divisin mittica


replicacin y segregacin de cromosomas
En la divisin de clulas eucariontes son
necesarios
Origen de replicacin
Centrmeros
Telmeros

Fase S y M del ciclo de divisin mittica


replicacin y segregacin de cromosomas
Origen de replicacin
Lugar donde se ensambla la maquinaria
de replicacin del ADN
Varios sitios ORI en eucariontes
Un solo sitio ORI en procariontes
Ubicado en regiones no codificadoras

Fase S y M del ciclo de divisin mittica


Duplicacin y segregacin de cromosomas
Centrmeros
Implicados en la correcta segregacin de los
cromosomas
Dirigen la formacin de un complejo proteico
denominado cinetocoro
Separa los cromosomas y los ubica en las
clulas hijas
Existe solo un centrmero por cromosoma
Tamao variable y presencia de secuencias de
ADN repetitivas

Molecular Biology of the Gene


Watson et al., 2004
Fifth Edition

Fase S y M del ciclo de divisin mittica


Duplicacin y segregacin de cromosomas
Telmeros
Ubicados en los extremos de los cromosomas
lineales
Unidos a varios protenas
Permiten reconocer los extremos naturales
de los cromosomas (protege de ADN
recombinacin y ADN degradacin)
Sitio ORI especial, permite replicar los
extremos de los cromosomas (telomerasa)

Ciclo celular
Intervalo G1 y G2 :
Checkpoints del ciclo celular
Le otorgan un tiempo de preparacin a
la clula para la etapa siguiente del
ciclo
Chequear que la fase previa del ciclo
se realiz de manera apropiada

Ciclo celular
Arresto del ciclo celular
Mutacin de genes importantes en la
regulacin del ciclo celular
Dao del ADN

Molecular Biology of the Gene


Watson et al., 2004
Fifth Edition

Importante la
participacin en el
ciclo celular de:
Kinasas
dependientes de
ciclina: CdKs
Ciclina
Ciclo celular
puede ser regulado
mediante
mecanismo que
regulen estas
protenas (prot
activadoras,
inhibidoras, CKIs)
Importante participacin de complejos proteicos SCF y APC

Divisin de la clula eucarionte


en dos clulas hijas con dos sets
de cromosomas idnticos
Mitosis

Divisin celular en organismos


superiores
Mitosis:
Desemsamblaje de la membrana nuclear de la
clula madre
Divisin de los cromosomas
Separacin de los cromosomas
Reensamblaje de la membrana nuclear
alrededor de los dos sets de cromosomas
Divisin final de la clula madre o citocinecis o
citoquinesis

Divisin celular en organismos


superiores
Mitosis:
Profase
Prometafase
Metafase
Anafase
Telofase
Citocinecis o citoquinecis

Molecular Biology of the Gene


Watson et al., 2004
Fifth Edition

Etapas fase M
(Mitosis)
Prometafase

Divisin
nuclear

Interfase G1-S-G2

Divisin
citoplasmtica

Divisin celular en organismos


superiores
Profase
Condensacin de los cromosomas
En el citoplasma se ensambla el huso mittico
entre los dos centrosomas
Final de la profase se desintegra la membrana
nuclear (descrito tambin en una etapa previa a
la metafase denominada prometafase)

Divisin celular en organismos


superiores
Prometafase
Comienza abruptamente con la desintegracin
de la membrana nuclear
Adhesin de los cromosomas al huso mittico a
travs del cinetocoro
Movimiento activo de los cromosomsa

Caractersticas:
Doble membrana
Espacio perinuclear
Lmina nuclear:
filamentos intermedios
Formada por
protena: laminina
Poros nucleares

Divisin celular en organismos


superiores
Metafase
Formacin de huso mittico
Adhesin del cinetocoro de las cromtidas
hermanas a los microtbulos
Adhesin bivalente
Formacin del plato metafsico

Molecular Biology of the Gene


Watson et al., 2004
Fifth Edition

Divisin celular en organismos


superiores
Anafase
Destruccin proteoltica de las molculas de
cohesina, por lo tanto prdida de la cohesin de
las cromtidas hermanas
Acortamiento de los cinetocoros
Movimiento de huso en los polos
Separacin de las cromtidas hacia polos
opuestos

Molecular Biology of the Gene


Watson et al., 2004
Fifth Edition

Divisin celular en organismos


superiores
Telofase
Prdida de la condensacin de los cromosomas
Formacin de la membrana nuclear alrededor
de los dos sets de cromosomas segregados
Comienzo de la divisin del citoplasma

Molecular Biology of the Gene


Watson et al., 2004
Fifth Edition

Divisin celular en organismos


superiores
Citocinecis
Citoplasma dividido en dos por medio de anillo
contrctil de filamentos de actina y miosina
Formacin completa de la envoltura nuclear
Excepcin:
Embrion de Drosophila, y algunas clulas de
mamferos (osteoclastos, trofoblastos, algunas
clulas hepticas y cardiacas) no ocurre la
citocinesis al final de la mitosis

Citocinesis

Regin media
Superposicin de
microtubulos

Anillo contractil

Divisin celular en organismos


superiores
Funcin Centrosomas
Organizacin de la cromatina
Sntesis y degradacin de la membrana nuclear durante
la divisin celular

Microtubulos del
huso mittico en
clulas animales

Microtubulos
astrales

Microtubulos
del cinetocoro

Microtubulos
que se
superponen

Divisin celular en organismos


superiores
Citocinesis en plantas
Debido a la presencia de la pared celular, el
citoplasma de la clula vegetal se divide desde
el interior mediante la formacin de la placa
celular entre los dos ncleos
Importante la participacin de microtbulos,
aparato de Golgi y fragmoplasto

Si no es controlado el ciclo celular, puede


derivar en alteraciones serias como cncer
Adems de duplicar el material gentico,
tambien deben duplicarse los organelos y
macromolculas
Clulas pueden permancer en G0 por largos
perodos, hasta que se produzca un estmulo
necesario que induzca a la clula a ingresar al
ciclo celular
Diferencias con levaduras
No se desintegra la membrana nuclear

Ciclo regulado, proceso de senescencia celular,


detencin de la divisin
Lneas celulares inmortales, divisin continua
Incorporacin de compuestos que indique si la
clula se encuentra en fase S:
Timidina titriada (3H-Timidina)
Bromo desoxiuridina (BrdU)

Figure 17-40. Effect of fresh medium on a confluent cell


monolayer. Cells in a confluent monolayer do not divide (indicated
in gray). The cells resume dividing (indicated in green) when
exposed directly to fresh medium. Apparently, in the undisturbed
confluent monolayer proliferation has halted because the medium
close to the cells is depleted of growth factors, for which the cells
compete.

Figure 17-44. Typical


signaling pathway for
stimulation of cell
proliferation by a growth
factor. This greatly
simplified diagram shows
some of the major steps. It
omits many of the
intermediate steps in the
relay system

Figure 17-45. The response of Myc to a growth factor. Myc is the


product of the early-response gene myc. The graph shows the changes
in the concentration of Myc protein following a sudden increase in
growth factor concentration to a new steady value, which causes the
cell to exit G0 and to proliferate. The changes in Myc concentration
reflect changes in myc gene transcription, stimulated by exposure of the
cell to the growth factor. Myc protein itself inhibits myc transcription,
and this negative feedback is thought to explain why the level of Myc
declines from its initial peak to a lower steady value

Meiosis

Meiosis
Ciclo de divisin meiotica posee G1, S y
una fase G2 prolongada
Durante la fase S se duplican los
cromosomas y las cromtidas permanecen
unidas
Apareamiento de cromosomas homlogos.
nico de la meiosis.
Recombinacin de cromosomas homologos

Meiosis
The first meiotic prophase is traditionally
divided into five sequential stages
Leptotene
Zygotene
Pachytene
Diplotene
and diakinesis

Figure 20-5. Events through the first cell


division of meiosis. For clarity, only one
pair of homologous chromosomes is
shown. The pairing of homologous
chromosomes (homologues) is unique to
meiosis. Each chromosome has been
duplicated and exists as attached sister
chromatids before the pairing occurs. As
shown by the formation of chromosomes
that are part red and part black, the
chromosome pairing in meiosis involves
crossing-over (genetic recombination)
between homologous chromosomes

Figure 20-6.
Comparison of meiosis
and normal cell
division. As in the
previous figure, only
one pair of homologous
chromosomes is
shown. In meiosis,
following DNA
replication, two nuclear
(and cell) divisions are
required to produce the
haploid gametes. Each
diploid cell that enters
meiosis therefore
produces four haploid
cells, whereas each
diploid cell that divides
by mitosis produces
two diploid cells.

Figure 20-7. Two major contributions to


the reassortment of genetic material
that occurs during meiosis. (A) The
independent assortment of the maternal
and paternal homologues during the
first meiotic division produces 2n
different haploid gametes for an
organism with n chromosomes.
Here n = 3, and there are 8 different
possible gametes. (B) Crossing-over
during meiotic prophase I exchanges
segments of homologous chromosomes
and thereby reassorts genes in
individual chromosomes. Because of
the many small differences in DNA
sequence that always exist between
any two homologues, both mechanisms
increase the genetic variability of
organisms that reproduce sexually.

Figure 20-8. Paired homologous


chromosomes during the transition to
metaphase of meiotic division I. A
single crossover event has occurred
earlier in prophase to create one
chiasma. Note that the four chromatids
are arranged as two distinct pairs of
sister chromatids and that the two
chromatids in each pair are tightly
aligned along their entire lengths as
well as joined at their centromeres.
The entire unit of four chromatids is
referred to as a bivalent.

Figure 20-9. Time course of chromo-some synapsis and desynapsis during meiotic
prophase I. A single bivalent is shown. The pachytene stage is defined as the
period during which a fully formed synaptonemal complex exists. In gametes of
female animals the subsequent diplotene stage is an enormously prolonged period
of cell growth during which the chromosomes are decondensed and very active in
transcription. This ends with diakinesis- the stage of transition to metaphase in
which the chromosomes recondense and transcription halts. In male gametes
diplotene and diakinesis are briefer and less distinct.

Figure 20-11. Comparison


of the mechanisms of
chromosome alignment (at
metaphase) and separation
(at anaphase) in meiotic
division I and meiotic
division II. The mechanisms
used in meiotic division II
are the same as those used
in normal mitosis

Figure 20-12. Comparison of times required for each of the stages of meiosis. Approximate
times for both a male mammal (mouse) and the male tissue of a plant (lily) are shown.
Times differ for male and female gametes (egg and sperm) of the same species, as well as
for the same gametes of different species. Meiosis in a human male, for example, lasts for
24 days, compared with 12 days in the mouse. Meiotic prophase I, however, is always
much longer than all the other meiotic stages combined

Figure 20-16. The stages of oogenesis. Oogonia


develop from primordial germ cells that migrate into
the developing gonad early in embryogenesis. After
a number of mitotic divisions, oogonia begin meiotic
division I, after which they are called primary
oocytes. In mammals primary oocytes are formed
very early (between 3 and 8 months of gestation in
the human embryo) and remain arrested in
prophase of meiotic division I until the female
becomes sexually mature. At this point a small
number periodically mature under the influence of
hormones, completing meiotic division I to become
secondary oocytes, which eventually undergo
meiotic division II to become mature eggs (ova).
The stage at which the egg or oocyte is released
from the ovary and is fertilized varies from species
to species. In most vertebrates oocyte maturation is
arrested at metaphase of meiosis II and the
secondary oocyte completes meiosis II only after
fertilization. All of the polar bodies eventually
degenerate. In most animals the developing oocyte
is surrounded by specialized accessory cells that
help isolate and nourish it (not shown).

In human males
meiosis and
spermatogenesis do
not begin in the
testes until puberty
and then go on
continuously in the
epithelial lining of
very long, tightly
coiled tubes, called
seminiferous
tubules.

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