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

 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)
S phase (6-8 hours):
•DNA replication → duplication of DNA;
•Chromosomes are bichromatid (2n=4c);
•Synthesis of histones;
•Duplication of centrioles.

DNA Chromosome
replication disjunction

S phase Anaphase

46 singlechromatid 46 bichromatid 46 singlechromatid 46 singlechromatid

chromosomes chromosomes 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
 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
 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
 Telophase and cytokinesis
•Decondensation of chromosomes
•Reorganization of nuclear envelope
•Reorganization of nucleoli
•Separation of cytoplasm (cytokinesis).
 Prophase
Prometaphase
Interphase
Metaphase
Telophase
Anaphase
 Nucleolar cycle

Metaphase

Telophase
Anaphase
Prophase
DNA
Preparation to mitosis Preparation to DNA replication replication

G2 Mitosis G1 S

Nuclear Nucleolus
envelope
Dissociation of nucleolus Formation of nucleolus
Centriolar cycle
 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

Transcription
Receptors Secondary
messengers factors
External
Oncogenes

Stimulators Inhibitors
Protooncogenes TSG (tumor
suppressor
genes)
 DNA repair

Cell cycle p53 C-myc Mitogens

Bcl-2

Apoptosis
Pro-onc TSG

Pro-onc TSG

Pro-onc
Cyclin В

Destroying of
Cyclins В

Destroying of
Cyclin А

Cyclins G1

Cyclin А
Destroying of
Cyclins G1
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, сdk2-cyclin A сdk1-cyclin A

D2, D3 сdk1-cyclin B

Restriction
poin
 Growth
Factor defactor
creştere
Receptor
Receptor

Cytoplasm
CITOSOL
Kinase
Kinaza 11

Kinase
Kinaza22

Gene Genă activată

activation de
by regulatory
proteina reglatoare
protein

Gena
Generăspunsului primar
of primary response

Gene of secondary response

Activation
Activarea of cellde
sistemului cycle control
control systemcelular
a ciclului
 Cell evolution after cell division

G1 G0 Apoptosis Transformation

S Differentiation
Malignisation
G2
Aging / death
Mitosis
Apoptosis
• Programmed cell death
• Physiological cell death
• Ensures control of equilibrium between
proliferation and cell death
 Signal

Этапы Living cell

апоптоза

High activity of nucleases

DNA fragmentation

Fragmentation of nucleus and

cell; formation of apoptotic bodies

Phagocytosis of apoptotic bodies

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.
 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