mitosis- Cell cycle and their check points

Topic is about the mitosis cell cycle

1. Cell cycle
Mitosis

2. Introduction to Mitosis
•Process of cell division in eukaryotes where a
single cell divides into two identical daughter
cells
•Crucial for growth, repair and asexual
reproduction in multi cellular organisms

3. Stages of cell cycle
Cell cycle
Interphase
G1SG2
Mitotic
phase
Mitotic division
ProphasePrometaphase Metaphase Anaphase Telophase
Cytoplasmic
division

4. G0 Phase
•The G0 phase - non-dividing state in the cell cycle
where cells are metabolically active(perform its
normal functions) but not actively preparing to
divide.
•It's a resting or quiescent phase that cells enter
from G1, usually due to factors like lack of
mitogens (cell division signals) or sufficient
energy.
•Cells in G0 can remain there indefinitely or
re-enter the cell cycle when conditions are
favorable.
•Nerve cells and heart cells are examples of cells
that often stay in G0 permanently.

5. Interphase
G1 phase:
•Cell growth occurs
•Cell gets ready for the next(S) phase
•Centrosome division starts
Checkpoint 1:
Cyclins check for any DNA damage
S phase:
•DNA replication occurs
•Centrosome duplication occurs

6. G2 Phase:
•Cell grows further
•Cell gets ready for the mitotic phase
Check point 2:
•Check for the proper replication of DNA

7. Interphase

8. Mitotic Division
(OR)
Karyokinesis
(OR)
Nuclear Division

9. Prophase

•DNA will already be loosely packed(or
relaxed) after replication(S Phase)
•Now, condensin protein will condense
the DNA into highly condensed form
•The identical chromosomes will be
attached at the centromere part by
cohesin protein forming sister
chromatids

10. Prophase
•The duplicated centrosomes will start moving to
the opposite poles by centrosome associated
motor proteins
•The microtubules from both centrosomes interact
with each other to form asters or basic mitotic
spindle apparatus at the point called foci
•Nucleolus disintegrates so that ribosome
production stops and the cell concentrates on cell
division rather than cell metabolism

12. Centrosome

13. Prometaphase
•The nuclear envelope breaks down and the
content of the nucleus will be released into
the cytoplasm
•The spindle fibres will be attached to the
kinetochores on the sister chromatids

15. Metaphase
•The sister chromatids will arrange at the imaginary
line at equal distance from both the poles forming the
metaphase plate or the equatorial plate at the centre

Checkpoint 3: (checkpoint after metaphase)
Also known as
•Spindle checkpoint
•The metaphase check point
•Anaphase-promoting complex (APC) checkpoint.
•This checkpoint ensures that all chromosomes are
correctly attached to the spindle microtubules before
the cell proceeds to anaphase.

16. Metaphase

17. Anaphase
Anaphase (very short phase):
•Separase enzyme will cleave cohesins and the
sister chromatids will be separated
•The microtubules will pull the each copy of
the chromatids to the poles
•The cell and the plasma will be elongated by
non kinetochore microtubules

18. Anaphase

19. Telophase
Telophase (last phase):
•The chromosomes at each pole will detach
from microtubules
•The nuclear membrane synthesis starts.
•Nucleolus reappears

21. Cytoplasmic Division
(OR)
Cytokinesis

22. Cytokinesis
•Cytokinesis is the final step in cell division where
the cytoplasm of a parent cell divides, resulting in
two separate daughter cells.
•Actin and myosin forms contractile ring at the
centre
•When the ring contracts the cleavage furrow
forms and deepens (forming intercellular bridge)
as the ring contacts further
•Abscission(separation or splitting) occurs and the
cells are separated

24. Mitosis overview

25. Significance of Mitosis
❖Growth and Development:
Mitosis is the primary mechanism by which multicellular
organisms grow and develop. As cells divide and multiply,
they contribute to the increase in size and complexity of
the organism.
❖Tissue Repair and Regeneration:
When tissues are damaged or worn out, mitosis provides
the means to replace the damaged cells with new,
genetically identical ones. This is vital for wound healing
and regeneration of lost or damaged body parts.
Ex: Regeneration of lizard tail

26. Significance of Mitosis
❖Asexual Reproduction:
In many unicellular organisms and some multicellular
organisms, mitosis serves as the basis for asexual
reproduction. This process produces offspring that are
genetically identical to the parent, allowing for rapid
population growth in favorable environments.
❖Maintenance of Chromosome Number:
Mitosis ensures that each daughter cell receives the
same number and type of chromosomes as the parent
cell. This is crucial for maintaining the genetic stability of
an organism across generations of cells.

27. Significance of Mitosis
❖Cell Replacement:
Many cells in the body have a limited lifespan and
are constantly being replaced through mitosis.
Ex: Red blood cells are continuously produced in
the bone marrow to replace those that have aged
and died.
❖Maintaining Nucleo-Cytoplasmic Ratio:
Mitosis also helps maintain the appropriate balance
between the volume of the nucleus and the
cytoplasm within a cell. This ratio is important for
proper cellular function.

28. Mitogens
•Mitogens are chemical agents, typically proteins or peptides, that
induce a cell to begin or accelerate the process of cell division
(mitosis). This process is known as mitogenesis.
Mitogen signaling:
•Receptor binding: The mitogen binds to a receptor on the cell's
surface.
•Signal cascade: The binding activates intracellular signaling
pathways.
•Gene transcription: The signal cascade leads to the activation of
certain transcription factors(TF)
•Cyclin expression: TF increases the transcription of G1 cyclins and
other genes necessary for the cell cycle.
•Phosphorylation of Rb: G1 cyclins partner with cyclin-dependent
kinases (Cdks) to form a complex that phosphorylates the
retinoblastoma protein (Rb).
•E2F release: The phosphorylation of Rb causes it to release the
E2F transcription factor.
•S-phase entry: Active E2F then initiates the transcription of genes
required for entry into the S phase (DNA synthesis) and cell
division.

29. Examples of mitogens
Animal mitogens:
•Platelet-Derived Growth Factor (PDGF): A protein
released from blood clots that stimulates cell
division in connective tissue cells, aiding in wound
healing.
•Epidermal Growth Factor (EGF): A
broad-specificity factor that promotes the division
of epithelial and other cell types.
•Lymphokines: Cytokines produced by
lymphocytes that act as mitogens for other
immune cells.
•Vascular Endothelial Growth Factor (VEGF): A
growth factor that directly induces cell
replication, particularly for the growth of new
blood vessels.

30. Examples of mitogens
Plant mitogens:
•Cytokinins: A class of plant hormones that
promote cell division in the shoots and roots.
•Gibberellins and auxins: Other plant hormones
that function as mitogens.
Other mitogens:
•Phytohemagglutinin (PHA): A plant-derived
protein often used in laboratory settings to
stimulate T-lymphocyte proliferation.
•Concanavalin A (Con A): Another plant lectin used
to promote the proliferation of T cells.
•Lipopolysaccharide (LPS): A component of the
outer membrane of gram-negative bacteria that
acts as a mitogen for B-lymphocytes

31. Mitogen Inhibitors
•Are inhibitors of the mitogen signaling pathways blocking
cellular proliferation, differentiation, and survival.
2 Types
❖MK inhibitors
❖MAPK inhibitors
MEK inhibitors:
•Mechanism: These inhibitors block mitogen-activated
protein kinase kinase (MEK1/2), which is upstream of the
ERK protein kinase.
•Examples: Selumetinib, trametinib, binimetinib, and
cobimetinib.
•Therapeutic Uses: Used to treat various cancers, including
melanoma, lung cancer, and low-grade serous ovarian
cancer, as well as plexiform neurofibromas.

32. Mitogen Inhibitors
p38 MAPK Inhibitors
•Mechanism: These inhibitors target the p38
mitogen-activated protein kinase and work by
competing for the ATP binding pocket.
•Examples: SB203580.
•Therapeutic Uses: Effective in models of
inflammation, arthritis, and septic shock.

33. Mitogen Inhibitors
MK-2 Inhibitors
•Mechanism: Block mitogen-activated protein
kinase-activated protein kinase 2 (MK-2), a kinase
downstream in the pathway.
•Therapeutic Uses: Shown to suppress TNFα
production and are relevant for treating
inflammatory conditions like rheumatoid
arthritis.
Other Inhibitors
•JNK Inhibitors: Compounds like SP600125 target
JNK kinases, which are also part of the MAPK
family.

34. Uses of mitogen inhibitors
•Melanoma and Lung Cancer
•Ovarian Cancer
•Exploring the use in hepatocellular carcinoma
(liver cancer), biliary cancer, and thyroid
cancer.
•Colorectal Cancer
•Rheumatic and Immune-Mediated Diseases
•Asthma
•Alzheimer's disease
•fibrotic diseases
•Intimal hyperplasia