Download Cell cycle

27.11.2014
Cell cycle
Cell cycle – a complement of genetic,
biochemical and morphological events from cell
birth till its division, differentiation or death
Normal cell cycle
Cell cycle during segmentation of zygote
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Human organism contains several types of
cells:
I. Highly-differentiated cells which have lost
their proliferation properties (nervous,
muscle, crystalline);
II. Differentiated cells with low proliferation
activity (liver cells, lymphocytes);
III. Non-differentiated cells with high
proliferation activity (STEM cells)
!!! Cell cycle = mitotic cycle
Steps of cell cycle
Interphase
G1 (postmitotic, presynthetic)
S (synthetic)
G2 (postsynthetic, premitotic)
Mitosis
Prophase, Prometaphase
Karyokinesis
Metaphase
Anaphase
Cytokinesis
Telophase
INTERPHASE
G1 – 6-12 hours:
•Decondensation of chromatin
•Transcription and translation
•Reorganization of nucleoli
!!! Chromosomes contain a single
chromatid
!!! Cells are diploid (2n=2c)
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S phase (6-8 hours):
•DNA replication → duplication of DNA;
•Chromosomes are bichromatid (2n=4c);
•Synthesis of histones;
•Duplication of centrioles.
DNA
replication
Chromosome
disjunction
S период
Анафаза
46 singlechromatid
chromosomes
46 bichromatid
chromosomes
46 singlechromatid 46 singlechromatid
chromosomes
chromosomes
G2 (3-4 hours) – preparation to cell
division:
•Control of quality of replication;
•Accumulation of tubulin;
•Accumulation of factors for cell division.
Quantity
Proteins
Synthesis
during
interphase
RNA
DNA
Hours
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Mitosis
Prophase
Metaphase
Anaphase
Telophase
Prophase
•DNA is replicated 2n=4c.
•Condensation of chromatin.
•Dissociation of nucleoli
•Dissociation of nuclear envelope
•Maturation of Kinetochore. Kinetochore –
a DNA-protein complex required for
attachment of mitotic spindle.
•Formation of mitotic spindle
Prometaphase
•Condensation of chromatin
•Movement of chromosomes to the middle of the
cell
•Attachment of mitotic spindle to kinetochore
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Metaphase
•Formation of metaphase plate
!!! All chromosomes are in the same plain at
equator
Anaphase
•Longitudinal cleavage of centromere
•Disjunction of chromatids and movement of
single-chromatid chromosomes to poles
!!! Speed of movement – 0,2-5,0 μm/min.
Duration of movement – 2-60 min. shortening
of microtubules from kinetochore site
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Telophase and cytokinesis
•Decondensation of chromosomes
•Reorganization of nuclear envelope
•Reorganization of nucleoli
•Separation of cytoplasm (cytokinesis).
Prophase
Interphase
Prometaphase
Metaphase
Telophase
Anaphase
G2
Mitosis
Telophase
Anaphase
Metaphase
Preparation to mitosis
Prophase
Nucleolar cycle
Preparation to DNA replication
G1
DNA
replication
S
Nuclear Nucleolus
envelope
Dissociation of nucleolus
Formation of nucleolus
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Centriolar cycle
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Control of cell cycle:
Control of passing from one stage to another.
Each event starts after previous event is ended.
Main events:
-
beginning of DNA synthesis
-
beginning of cell division.
Beginning of each main event take place after
passing a restriction point:
R1 – G1 / S
R2 – G2 / Mitosis
Restriction points:
R1 – G1 / S
R2 – G2 / Mitosis
Check points:
I – G1 (checking of cell grow, environment
factors)
II – G2/Mitosis (checking of cell grow,
environment factors, quality of replication)
III – Metaphase (checking if mitotic spindle is
attached correctly).
Factors of control of cell cycle
Receptors
Transcription
factors
Secondary
messengers
External
Oncogenes
Stimulators
Inhibitors
Protooncogenes
TSG (tumor
suppressor
genes)
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DNA repair
Cell cycle
p53
Mitogens
C-myc
Bcl-2
Apoptosis
Pro-onc
TSG
Pro-onc
TSG
Pro-onc
DNA synthesis
Mitosis
End of
mitosis
Control of
cell
structure
End of
mitosis
Control of
DNA
integrity
Control of
DNA
replication
Synthesis of cyclins
Degradation of cyclins
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Cyclin В
Destroying of
Cyclins В
Destroying
of Cyclin А
Cyclins G1
Cyclin А
Destroying of
Cyclins G1
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Cyclins – proteins that control cell cycle:
1. Destroy the previous stage complex
2. Ensure activity of actual stage complex
3. Activate next stage complex
сdk2-cyclin Е
сdk2-cyclin D1,
D2, D3
сdk2-cyclin A
сdk1-cyclin A
сdk1-cyclin B
Restriction
poin
Growth
factor
Factor
de creştere
Receptor
Receptor
Cytoplasm
CITOSOL
Kinase1 1
Kinaza
Kinaza 22
Kinase
Genăactivation
activată de by
Gene
proteina reglatoare
regulatory
protein
Gena of
răspunsului
primar
Gene
primary response
Gene of secondary response
Activarea
sistemului
control
a ciclului
celular
Activation
of cell de
cycle
control
system
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Cell evolution after cell division
G1
S
G0
Apoptosis
Transformation
differentiation
Malignisation
G2
Aging/ death
Mitosis
Apoptosis
 Programmed
cell death
 Physiological cell death
 Ensures control of equilibrium
between proliferation and cell death
Signal
Этапы
апоптоза
Living cell
High activity of nucleases
DNA fragmentation
Fragmentation of nucleus and
cell; formation of apoptotic bodies
Phagocytosis of apoptotic bodies
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Molecular mechanisms in apoptosis

Receiving of signals by receptors

Transfer of signal to transcription
factor р53

Increasing of mitochondrial
membrane permeability due to
interaction of p53 with bcl-2 gene

Activation of caspase cascade
and proteolysis

Activation of endonucleases and
nuclear fragmentation

Cell fragmentation and formation
of apoptotic bodies

Phagocytosis of apoptotic bodies
Apoptotic pathway is characteristic for:





Mutant cells, transformed cells
Old cells
Cells recognized as foreign → abnormal
receptors
Cells which have lost contacts with
neighbors cells
Excessive cells → for control of cell number.
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Normal apoptosis
During embryogenesis – organ modeling
Elimination of rudimental organs
 Elimination of aged cells
 Elimination of tumor cells
 In immune system → elimination of
unwonted clones


Diseases associated with
defective apoptosis
Cancers
Autoimmune diseases
 Viral diseases


Diseases associated with excessive apoptosis
Neurodegenerative diseases
- Alzheimer disease
- Parkinson disease
- retinita pigmentosum
 Ischemic diseases
- heart failure
- stroke
 Osteoporosis
 AIDS

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