Premedical - biology
Mitosis and Cell cycle
G ~ Gap/GrowthCell cycleS ~ DNA sythesis
• M phase and interphase
• M phase: Mitosis and cytokinesis
• Interphase : G1, S, G2 phase
• 46 chromosomes, 23 chromosomes from each
parent
• distributes identical sets of 46 chromosomes
to daughter cells
The cell cycle
2n
2n
2n
• Internal an external cues help regulate the
cell cycle
• cancer cells have escaped from cells
cycle controls
• mitosis evolved from binary fission in
bacteria
• somatic cell in proliferation state
Cell cycle
Physiological modes of somatic cell
proliferationcell cycle
resting cellsG0 phase
Proliferation in: ontogenesis physiological renewal of cells reparation and wound healing immune response
Resting (Quiescent) Cells: G0
G0 phase relates
to terminal stages of
differentiation
e.g. hepatocytes divide
1 / year;
neurons, myocytes
do not divide;
epithelial cells divide 1-2 / day
Mitotic spindle
• Fibers made of microtubules
• the spindle elongate by incorporating subunits of
the protein tubulin
• it starts from centrosome – centrioles -
microtubule organizing center
Centrosomes and Centriolas
• 9 set of triplets microtubules
• tubulin α, β => microtubules
• grow out from a centrosome, within of animal
cells are a pair of centriolas
• cell shape, cell motility, cell division, organelle
movements
• spindle: Cenrosomes, microtubules, asters
• kinetochore – proteins
and chromosomal DNA
at the centromere
• Kinetochore
microtubules
• polar microtubules
• methaphase plate
Mitosis – animal cells
Interphase: one or more nucleoli, centrosome
replicates, in animal features to pair of
centriolas, chromosomes are already
duplicated
Prophase: chromatin fibers are coiled, nucleoli
disappear, mitotic spindle begins to form
Prometaphase: nuclear envelope fragments, mitotic
spindle interact with chromosomes,
chromosomes condensation
Metaphase: spindle poles are at opposite sides,
chromosome are on the metaphase plate,
each chromosome is attached by kinetochore
to mitotic spindle
Anaphase: chromatids moving towards opposite
poles of the cell, kinetochore mictotubules
shorten, the poles move farther apart, at the
end two poles have two collection of
chromosomes
Telophase: non-kinetochore microtubules elongate
and form daughter nuclei, nuclear envelope
arise, cytokinesis runs
MG1
S
G2
Schematic view of
chromosome pair –
homologous
chromosomes - during
cell cycle
chromosomes
in G1 - 1 chromatid
in G2 - 2 chromatids
Cytokinesis
Cleavage
• contractile ring of actin microfilaments interacts
with myosin
• cell plate in plant cells
Cell Cycle G1 phase – the longest and the most variable part
of the cell cycle
■ Growth of the cell
■ completion of organelles (ribosomes,
mitochondria, endoplasmic reticulum etc.)
■ RNA and protein synthesis
■ synthesis of nucleotides, preparation for
replication
S phase – replication of nuclear DNA
extranuclear DNA replicates during the whole
interphase
G2 phase – cell growths, protein synthesis, RNA,
creation of cell structures
M phase:
Mitosis - division of the nucleus
Cytokinesis – division of the cell
Control system of cell cycle
Cyclin – cyclic accumulation and degradation
during the cell cycle
Cdk – cyclin dependent kinases (CDK)
= enzymes that phosphorylate other proteins,
activated by cyclin
complex cyclin / kinase => protein
phosphorylation => triggers cell cycle phases
Maturation promoting factorM-phase promoting factor
Check points
Set of molecules operates in the cell, they triggers
and coordinate key events
Checkpoints are critical points,
where signals can stop or
go-ahead the cell cycle:
G1 checkpoint
G2 checkpoint
M checkpoint
Cell cycle checkpoints: G1 – enter into S – restriction point, active
complex phosphorylates Rb protein
– beginning of S phase
G2 – enter into M – complex phosphorylates
histons and some of the components of cytoskelet
(= chromosomes condensation, disintegration of the
nuclear envelope, microtubules remodeling and
other changes related to mitosis)
Genes regulating cell cycle:
Protooncogenes products stimulate cell division
Genes for growth factors, receptors, regulatory
proteins etc.
mutated forms = oncogenes => permanent or
increased mitotic activity
(effect of one allele mutated)
Ras gene
Tumor suppressor genes (TSG)antioncogenes
products inhibit mitotic division
effect of both allele mutated
Rb1 gene, product RB protein Mutations in retinoblastom and other tumors
TP 53 gene, p53 product – induction of DNA
repair or apoptosis = programmed cell death mutations in many tumors
Carcinogenesis
Mutator genes – genes for reparation enzymes
The proteins encoded by many proto-oncogenes
and tumor-suppressor gene are components of
cell-signalling pathways.
Multistep model of cancer development
Aging (senescence) limited number of cell division (maximum 50)
Hayflick’s limit
both in vivo and in vitro
accumulation of mutations
decreased cytokines response, increased
synthesis of inhibitory proteins
Apoptosis = programmed cell death
final stage of aging process in cell
elimination of cells, which can not be repaired
during embryogenesis - reduction of redundant
parts
some diseases
Purpose: elimination of cells, that fulfilled their
fate and could become destructive for the
organism
Importance of apoptosis in ontogenesis
Apoptosis: without disintegration of both plasma membrane
and organelles chromatin condensation, surface blebbing, cell
fragmentation apoptotic bodies fagocytosis without inflammation
Necrosis: disruption of plasma membrane
and organelles, release of the cell content into
extracelular space inflammation
Apoptosis of a human blood cell
Thank youThank youfor your attentionfor your attention
Campbell, Neil A., Reece, Jane B., Cain Michael L., Jackson, Robert B., Minorsky, Peter V., Biology, Benjamin-Cummings Publishing Company, 1996 –2010.