Transcript Nucleus Structure and Cell Cycle

Nucleus Structure
and Cell Cycle
Dr.rer.nat., Dra. Asmarinah, MS
Depart of Medical Biology
Faculty of Medicine University of Indonesia
The structure of cells
a
b
Schematic diagrams of
a. “generalized” bacterial cell
b. Plant cell
c
c. Animal cell
Nucleus
-The biggest organell of the cell
-Contains the main genome that is
packaged in chromosomes
-The principal site of DNA and RNA
synthesis
Nucleus’s structure
A. Electron micrograph of thin section through the nucleus of
human fibroblast
B. Schematic drawing of the nucleus
Nuclear envelope: double membrane surrounding the
nucleus (outer and inner membrane) and is perforated by
nuclear pore that allow selected molecules to move
between nucleus and cytoplasma
Nuclear lamina: Fibrous meshwork of protein on inner
surface of inner nuclear membrane. It is made up of
anetwork of intermediate filament
Nucleolus: structure in nucleus where rRNA is
transcribed and ribosomal subunits are assembled
Function of the
nucleolus in
ribosome and other
ribonucleoprotein
synthesis
Nucleolus, large aggregate of macromolecules, contain:
 rRNA genes, precussors rRNA, mature rRNA, rRNAprocessing enzymes, snoRNAs, ribosomal protein.
Other nuclear bodies:
a. Cajal bodies
b. Gemini of Cajal bodies (GEMS
c. “Speckles” (interchromatin granule clusters)
a and b: may be sites where snRNPs are recycled, or
reseting of RNA
c: as a stockpiles of fully mature snRNPs other RNA
processing component
Nuclear matrix or scaffold:
Insoluble materials that are formed by
protein and RNA molecules, left in
nucleus after a series of biochemical
extraction steps
Cell cycle and
division
2 main stages in the cell cycle:
1. Chromosome/DNA replication or duplication
Occur during S phase (S = synthesis)
2. Chromosome segregation
Occur in M phase (M = mitosis)
Between these phase there are G phase (G = Gap) which in the cell
require more time to monitor the environment and to grow and double
their mass
G1: Between M phase and S phase
to monitor the internal and external environment to ensure that
conditions are suitable and preparations are complete for entering
the next phase
G2: Between S phase dan M phase
to grow and double their proteins and organelles before the
entering M phase
Cell cycles in vivo
Depends on the capacity to divide, there are 3 categories
of cells:
1. Cells that lack the ability to divide and are highly
specialized, Examples: nerve cells, muscle cells or red
blood cells
2. Cells that normally don’t divide but can be induced to
divide when given an appropriate stimulus. Examples:
liver cells, lymphocytes
3. Cells that normally posses a relatively high level of
mitotic activity. Examples: spermatogonia,
hematopoietic stem cells and cells at the base of the
epithelia that line the body cavities and the body
surface
Cell cycle control system
Play a role in the regulation of the amount of the cell in
tissue
Aim:
- to respon and to monitor the internal and eksternal
environment for the continuing of the cell cycle.
- to trigger and control the major process of the cell cycle,
i.e: DNA replication, nuclear and cytoplasmic division
Control system in the cell cycle
The control system can
arrest the cell cycle at
specific checkpoints
“Checkpoint system” in the cell cycle
1. G1 “checkpoint”
Occur at the end of
the G1 phase
before entering S
phase
2. G2 “checkpoint”
at the end of G2
phase before M
phase
3. Metafase
“checkpoint”
at the end of
metaphase in
mitosis to enter
anaphase.
2 key components of the cell cycle control
system:
1. Cyclins
will be synthezed dan destroyed in each cell cycle
2. “Cyclin-dependent kinase” (CdK)
Protein kinases that its activity rise and falls during the
cell cycle.
CdK level are constant in the cell cycle
Without Cyclin, CdK enzyme inactive
Combination of
two key
component in
the control
system of the
cell cycle
4 combination of the cyclin and CdK in the cell cycle
and their function
1. G1-cyclin (cyclin D) + CdK = G1-CdK
helps promote passage through Start or the restriction point in
late G1.
2. G1/S-cyclin (cyclin E) + CdK = G1/S-CdK
Commit the cell to DNA replication .
3. S-cyclin (cyclin A) + CdK = S-Cdk
required for the initiation of DNA replication.
production DNA polimerase
The activity of S-CdK still high during G2 and begin M 
prevent rereplication
Continued
4. M-cyclin (cyclin B) + Cdk = M-Cdk
M-Cdk promote the event of mitosis, i.e:
- phosphorilation of kondensin to changes of the DNA coiling in
chromosom condensation process
- phosphorilation of lamin, to digest of nuclear lamina for the
breaking of nuclear membrane
- phosphorilation of kinesin, play a role in the formation and the
function of spindel fiber; as well as katastropin and
microtubule-associated protein for the stabilization of microtubule
- activation of APC (“Anaphase Promoting Complex), for digestion
of kohesin in the chromosome segregation process
DNA damage checkpont in the cell cycle
• At the end of G1 phase
prevent entry into S phase. DNA damage leads to the
activation of the gene regulatory protein p53 which
stimulates the trancription of several genes such as p21.
This protein inhibits the activity of G1/S-CdK dan S-CdK.
• At the end of G2 phase
DNA damage inactivate the phosphatase CDc25 that it
can blocks the phosphorilation and activation of M-CdK,
thereby blocking entry into mitosis.
When the DNA damage is repaired, the inhibitory signal
is turned off, and cell-cycle progression resumes.
“DNA damage checkpoint”
At the end of G1 phase
Cell division
•Bacteria
- Compared
to the complex steps of mitosis, the process of
cell division of bacteria is much simpler.
- Sometime
early in the bacteria's life, a second copy of its
DNA is made. At the replication origin, which is a specific site
on the chromosome. The two copies are attached side by side
to the cell membrane.
-Cell division of bacteria called binary fission. Binary fission
is division in which the cell pinches itself in two, creating two
equal or nearly equal halves.
Sequential events of cell division in bacteria:
- Between
the two attached DNA genomes, a new plasma
membrane and cell wall components are built.
-As new materials continue to be added on, the cell is slowly
pinched in two by the plasma membrane, pushing inward.
Because the location where the cell constriction starts is
between the two DNA copies, each daughter cell is ensured
one copy.
- the
cell is divided and a new cell wall forms around the new
membrane, creating two cells from one.
• Eukaryotic cell
Consist of two events, i.e:
1. Nuclear division (kariokinesis)
- Profase
- Prometafase
- Metafase
- Anafase
- Telofase
2. Cytoplasmic division (cytokinesis)
If it doesn’t happened, leads multinucleated cell.
Interphase
During interphase,
- increasing of the cell size
- DNA replication
- Duplication of the centrosome
Prophase
-Replicated chromosome that
contains two closely associated
sister chromatid, condense
- the mitotic spindle assambles
between the two centrosome which
have replicated and moved to apart
in the outside of nucleus
-Nuclear membrane still intake
Prometaphase
- Breakdown of the nuclear envelope
-Chromosomes can attach to spindle
microtubule via their kinetochores and
undergo active movement
Metafase
-The chromosomes are aligned at
the equator of the spindle, midway
between the spindle poles.
- Kinetochore microtubules attach
sister chromatids to opposite poles
of the spindle
Anaphase
-The sister chromatid
synchronously separate to form
two daugther chromosomes, and
each is pulled slowly towards the
spindle pole it face.
-Kinetochore microtubules get
shorter, and the spindle poles also
move apart; both processes
contribute to the chromosome
separation
Telophase
-The two sets of daughter
chromosomes arrive at the poles of
the spindle and decondense
- A new nuclear envelope
reassembles around each set,
completing the formation of two nuclei
and marking the end of mitosis
-The division of the cytoplasm begins
with the assembly of the contractile
ring.
Cytokinesis
-The cytoplasm is divided in
two by a contractile ring of
actin and myosin filament,
which pinches the cell in two to
create two daughters, each
with one nucleus
Meiosis
= “reduction” (Greek word)
-ensure of production of haploid phase in the life cycle
-Divided into:
* meiotic division I : each chromosome (consisting of
two chromatid) is separated from its homologue
* meiotic division II : two chromatid of each
chromosome are separated from one another
- By mixing maternal and paternal (recombinant) allele
between homologue chromosomes at the profase I,
result in increasing of the genetic variability of
organism from one generation to the next, with novel
ge
Spermatogenesis
Oogenesis
Stages in primary spematocyte
-Leptotene: chromosome become visible in the light
microskope. In the electrone microscope, chromosome are
revealed to be composed of paired chromatids
-Zygotene: is marked by the visible association of
homologous with one another. This process of chromosome
pairing is called by synapsis
-Pachytene: is caharacterized by a fully formed synaptonemal
complex (SC), i.e: a ladder-like structure with tranverse
protein filament connecting the two lateral element
-Diplotene: is recognized by the dissolution of SC, which
leaves the chromosome attached to one another at specific
point, termed chiasmata
-Diakinesis: the meiotic spindle is assembled and the
chromosome are prepared for separation
Extracellular control of cell division, cell
growth, and apoptosis
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

Mitogen, stimulate cell division that otherwise block progress
through the cell cycle.
Growth factor, stimulate cell growth (an increase in cell mass) by
promoting the synthesis of proteins and other
macromolecules and by inhibiting their degradation
Survival factor, promote cell survival by suppresing apoptosis
References:
Albert et al., Molecular Biology of the Cell. Garland Scientific. 5th
ed. 2008.
Karp G. Cell and Molecular Biology. 4th ed. 2005
Lodish et al, Molecular Biology of the Cell. 5th ed. 2008