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Chromosome
duplication
(including DNA
synthesis)
Centromere
Sister
chromatids
Separation
of sister
chromatids
Sites of mitosis
In the foetus, babies and growing children mitosis occurs in
most tissues.
Muscle cells
nuclei (cells in G2) and binucleate cells (cells that have not yet
undergone cytokinesis).
The rate of cell division varies with the need for those
types of cells.
Cell type
Skin cells
24 hour- 2 weeks
RBCs
hepatocytes
Intestinal lining cells
120 days
300-500 days
4-5 days
Interphase
ATP is synthesized.
Damaged parts are repaired.
Wastes are excreted.
Proteins are made.
Organelles are formed.
Chromosomes are copied.
Specialized tasks are performed .
Mitosis
1. Prophase
Longest phase.
Chromatin coils.
Nucleus disappears.
Centrioles migrate.
Spindle forms.
1.
2.
3.
4.
5.
6.
Prophase
Prometaphase
metaphase
Anaphase
Telophase
Cytokinesis
Prometaphase
Metaphase
Anaphase
Centromere splits.
Chromatids are separated.
Chromatids are now called
chromosomes.
Telophase
Cytoplasm divides.
Nucleus reappears.
Chromosomes uncoil.
Cytokinesis
The cytoplasm divides and two identical
daughter cells are formed.
G2/M
has DNA synthesis been
completed correctly?
commitment to mitosis
spindle checkpoint
are all chromosomes attached
to spindle?
can sister chromatids separate
correctly?
G1/S checkpoint
G1/S checkpoint is most critical
primary decision point
restriction point
G0 phase
G0 phase
non-dividing, differentiated state
most human cells in G0 phase
liver cells
M
Mitosis
G2
Gap 2
S
Synthesis
G1
Gap 1
G0
Resting
Go-ahead signals
Protein signals that promote cell growth &
division
internal signals
promoting factors
external signals
growth factors
Primary mechanism of control
phosphorylation
kinase enzymes :- activates cell signals
inactivated Cdk
activates proteins
Cdk-cyclin complex - triggers passage through
different stages of cell cycle
activated Cdk
Cdk
Degraded
cyclin
G2
checkpoint
Cyclin is
degraded
MPF
Cdk
Cyclin
Spindle checkpoint
G2 / M checkpoint
Chromosomes attached at
metaphase plate
Replication completed
DNA integrity
Inactive
Active
Inactive
Cdk / G2
cyclin (MPF)
Active
APC
cytokinesis
mitosis
G2
G1
S
MPF = Mitosis
Promoting Factor
APC = Anaphase
Promoting Complex
Cdk / G1
cyclin
Active
G1 / S checkpoint
Inactive
Growth factors
Nutritional state of cell
Size of cell
External signals
Growth factors
coordination between cells
protein signals released by body cells that
stimulate other cells to divide
density-dependent inhibition
crowded cells stop dividing
each cell binds a bit of growth factor
not enough activator left to trigger division in
any one cell
anchorage dependence
to divide cells must be attached to a substrate
touch sensor receptors
Oncogenes
Development of Cancer
Cancer develops only after a cell experiences ~6 key mutations hits)
1. Unlimited growth
Turn on growth promoter genes
2. Ignore checkpoints
Turn off tumor suppressor genes
(p53)
3. Escape apoptosis
Turn off suicide genes
Clinical Applications
Chemotherapy of cancers:
Interrupting the cell cycle and preventing the cancer cells from
proliferating.
They are:
1. Cell cycle-specific (CCS): Act specifically on tumor cells
undergoing cycling)
i. Usually more active in a specific phase of the cell cycle.
ii. Particularly effective when large proportion of tumor
cells are proliferating.
OR
2. Cell cycle-non-specific (CCNS): Kill tumor cells in both
cycling and resting phases of the cell cycle.
Clinical Applications
Side effects:
The normal sites of cell proliferation are affected resulting in:
hair loss
intestinal disorders
anaemia
infertility