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.