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The cell cycle The cell cycle The life of a cell from its formation to its division The cell cycle The big picture A walk through the cell cycle Control of the cell cycle Cancer: a lack of control of the cell cycle The big picture “Every cell from a cell”-Rudolf Virchow

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the cell cycle2

The cell cycle

The life of a cell from its

formation to its division

the cell cycle3

The cell cycle

  • The big picture
  • A walk through the cell cycle
  • Control of the cell cycle
  • Cancer: a lack of control of the cell cycle
the big picture
The big picture
  • “Every cell from a cell”-Rudolf Virchow
  • The continuity of life is based on reproduction of cells, cell division
  • Cell division results in genetically identical daughter cells
  • Unicellular organisms use cell division as a means of reproduction (asexual reproduction)
  • Sexually reproducing organisms develop from a fertilized egg via cell division
  • In multicellular organisms, cell division is critical to growth and repair
a walk through the cell cycle
A walk through the cell cycle

What happens?

  • DNA, which is arranged in chromosomes, duplicates
  • Each daughter cell receives the full genome
  • Cytoplasm divides
a walk through the cell cycle prokaryotes

Cell wall

Origin of

replication

Plasma

membrane

E. coli cell

Bacterial

chromosome

Two copies

of origin

Origin

Origin

A walk through the cell cycle: Prokaryotes
  • Cell division begins when the chromosome begins to divide
  • One copy moves to one pole, the other copy moves to other end of the cell
  • The cell elongates
  • Replication of the DNA is completed, the plasma membrane moves inward and the cell wall develops
  • This is asexual reproduction (binary fission)
a walk through the cell cycle prokaryotes7

Cell wall

Origin of

replication

Plasma

membrane

E. coli cell

Bacterial

chromosome

Two copies

of origin

Origin

Origin

A walk through the cell cycle: Prokaryotes

This process is more complicated in eukaryotes

  • Cell division begins when the chromosome begins to divide
  • One copy moves to one pole, the other copy moves to other end of the cell
  • The cell elongates
  • Replication of the DNA is completed, the plasma membrane moves inward and the cell wall develops
  • This is asexual reproduction (binary fission)
a walk through the cell cycle eukaryotes

INTERPHASE

S

(DNA synthesis)

G1

Cytokinesis

G2

Mitosis

MITOTIC

(M) PHASE

A walk through the cell cycle: Eukaryotes
  • The cell cycle involves:
  • Interphase
    • Growth and DNA duplication
  • M-phase
    • Mitosis-division of the nucleus
    • Cytokinesis-division of the cytoplasm

DNA molecules

a walk through the cell cycle eukaryotes9

INTERPHASE

S

(DNA synthesis)

G1

Cytokinesis

G2

Mitosis

MITOTIC

(M) PHASE

A walk through the cell cycle: Eukaryotes
  • The cell cycle involves:
  • Interphase
    • Growth and DNA duplication
  • M-phase
    • Mitosis-division of the nucleus
    • Cytokinesis-division of the cytoplasm

DNA molecules

Let’s watch a movie about this!

a walk through the cell cycle duplication of genetic information during eukaryotic cell division
A walk through the cell cycle: Duplication of genetic information during eukaryotic cell division

Interphase:

  • The cell grows during G1
  • The chromosomes are duplicated during S phase
    • Unlike proks, they have many!
    • When the cell is not dividing (even as it duplicates its DNA) the chromosomes are long and thin
    • After duplication the chromosomes are shorter and thicker
    • Each duplicated chromosome has two identical sister chromatids (attached at the centromere)
    • Each will become a chromosome in the new daughter cells

0.5 µm

Chromosomes

DNA molecules

Chromosome

duplication

(including DNA

synthesis)

Centromere

Separation of

sister chromatids

Sister chromatids

Centromere

a walk through the cell cycle g2 phase interphase

Metaphase

Anaphase

Telophase and Cytokinesis

G2 of Interphase

Prophase

Prometaphase

Centrosomes

(with centriole

pairs)

Early mitotic

spindle

Centromere

Chromatin

(duplicated)

Fragments

of nuclear

envelope

Nonkinetochore

microtubules

Aster

Cleavage

furrow

Metaphase

plate

Nucleolus

forming

Daughter

chromosomes

Nuclear

envelope

forming

Centrosome at

one spindle pole

Spindle

Nuclear

envelope

Kinetochore

Chromosome, consisting

of two sister chromatids

Kinetochore

microtubule

Plasma

membrane

Nucleolus

A walk through the cell cycle: G2 phase (Interphase)

During the G2 phase of interphase:

-Nuclear envelope is still intact (nucleoli are still visible)

-Centrosomes have formed

-Duplicated chromosomes cannot be seen

a walk through the cell cycle mitosis

Metaphase

Anaphase

Telophase and Cytokinesis

G2 of Interphase

Prophase

Prometaphase

Centrosomes

(with centriole

pairs)

Early mitotic

spindle

Centromere

Chromatin

(duplicated)

Fragments

of nuclear

envelope

Nonkinetochore

microtubules

Aster

Cleavage

furrow

Metaphase

plate

Nucleolus

forming

Daughter

chromosomes

Nuclear

envelope

forming

Centrosome at

one spindle pole

Spindle

Nuclear

envelope

Kinetochore

Chromosome, consisting

of two sister chromatids

Kinetochore

microtubule

Plasma

membrane

Nucleolus

A walk through the cell cycle: Mitosis

Prophase:

-Chromosomes condense and are visible (nucleoli disappear)

-Mitotic spindle begins to form (contains centrosomes, aster, and microtubules)

-Centrosomes move away from each other

a walk through the cell cycle mitosis13

Metaphase

Anaphase

Telophase and Cytokinesis

G2 of Interphase

Prophase

Prometaphase

Centrosomes

(with centriole

pairs)

Early mitotic

spindle

Centromere

Chromatin

(duplicated)

Fragments

of nuclear

envelope

Nonkinetochore

microtubules

Aster

Cleavage

furrow

Metaphase

plate

Nucleolus

forming

Daughter

chromosomes

Nuclear

envelope

forming

Centrosome at

one spindle pole

Spindle

Nuclear

envelope

Kinetochore

Chromosome, consisting

of two sister chromatids

Kinetochore

microtubule

Plasma

membrane

Nucleolus

A walk through the cell cycle: Mitosis

Prometaphase:

-The nuclear envelope fragments

-Microtubules attach to the chromatids (at the kinetochores)

-Chromosomes are jerked back and forth

-Other microtubules interact (connecting from different poles)

a walk through the cell cycle mitosis14

Metaphase

Anaphase

Telophase and Cytokinesis

G2 of Interphase

Prophase

Prometaphase

Centrosomes

(with centriole

pairs)

Early mitotic

spindle

Centromere

Chromatin

(duplicated)

Fragments

of nuclear

envelope

Nonkinetochore

microtubules

Aster

Cleavage

furrow

Metaphase

plate

Nucleolus

forming

Daughter

chromosomes

Nuclear

envelope

forming

Centrosome at

one spindle pole

Spindle

Nuclear

envelope

Kinetochore

Chromosome, consisting

of two sister chromatids

Kinetochore

microtubule

Plasma

membrane

Nucleolus

A walk through the cell cycle: Mitosis

Metaphase:

-Centrosomes are now at opposite poles

-Chromosomes are lined up on the metaphase plate

-All chromosomes are attached to each of the poles

a walk through the cell cycle mitosis15

Metaphase

Anaphase

Telophase and Cytokinesis

G2 of Interphase

Prophase

Prometaphase

Centrosomes

(with centriole

pairs)

Early mitotic

spindle

Centromere

Chromatin

(duplicated)

Fragments

of nuclear

envelope

Nonkinetochore

microtubules

Aster

Cleavage

furrow

Metaphase

plate

Nucleolus

forming

Daughter

chromosomes

Nuclear

envelope

forming

Centrosome at

one spindle pole

Spindle

Nuclear

envelope

Kinetochore

Chromosome, consisting

of two sister chromatids

Kinetochore

microtubule

Plasma

membrane

Nucleolus

A walk through the cell cycle: Mitosis

Anaphase:

-The connection between chromatids at the centromere is cleaved (each chromatid is now a chromosome)

-Chromosomes are pulled to opposite poles

-The cell elongates

-Anaphase ends when the chromosomes reach the poles

a walk through the cell cycle mitosis16

Metaphase

Anaphase

Telophase and Cytokinesis

G2 of Interphase

Prophase

Prometaphase

Centrosomes

(with centriole

pairs)

Early mitotic

spindle

Centromere

Chromatin

(duplicated)

Fragments

of nuclear

envelope

Nonkinetochore

microtubules

Aster

Cleavage

furrow

Metaphase

plate

Nucleolus

forming

Daughter

chromosomes

Nuclear

envelope

forming

Centrosome at

one spindle pole

Spindle

Nuclear

envelope

Kinetochore

Chromosome, consisting

of two sister chromatids

Kinetochore

microtubule

Plasma

membrane

Nucleolus

A walk through the cell cycle: Mitosis

Telophase:

-Two daughter nuclei form in the cell (nuclear envelope forms and nucleoli appear)

-Chromosomes become less dense

-Mitosis is complete

a walk through the cell cycle cytokinesis

100 µm

Cleavage furrow

Daughter cells

Contractile ring of

microfilaments

(a) Cleavage of an animal cell (SEM)

A walk through the cell cycle: Cytokinesis

Cytokinesis

-Usually occurs during late telophase

-In animal cells, it occurs by cleavage

-A cleavage furrow forms

-Actin microfilaments and

myosin motor proteins cause it

to contract

a walk through the cell cycle cytokinesis18

Vesicles

forming

cell plate

Wall of

parent cell

1 µm

Cell plate

New cell wall

Daughter cells

(b) Cell plate formation in a plant cell (TEM)

A walk through the cell cycle: Cytokinesis

Cytokinesis

-Usually occurs during late telophase

-In plant cells, the cell wall must be constructed

-cell plate is formed

-it develops into a cell wall

a walk through the cell cycle in review

INTERPHASE

S

(DNA synthesis)

G1

Cytokinesis

G2

Mitosis

MITOTIC

(M) PHASE

A walk through the cell cycle: In review
  • The cell cycle involves:
  • Interphase
    • Growth and DNA duplication
  • M-phase
    • Mitosis-division of the nucleus
    • Cytokinesis-division of the cytoplasm

DNA molecules

control of the cell cycle
Control of the cell cycle
  • Some cells divide more than others
  • Timing and rate of cell division are highly regulated
control of the cell cycle21
Control of the cell cycle
  • Some cells divide more than others
  • Timing and rate of cell division are highly regulated

How is the cell cycle regulated?

control of the cell cycle22
Control of the cell cycle

Evidence for cytoplasmic signals (Johnson and Rao 1970)

EXPERIMENT

Experiment 1

Experiment 2

G1

S

G1

M

RESULTS

M

S

S

M

control of the cell cycle23

5

30

4

20

3

% of dividing cells (– )

Protein kinase activity (– )

2

10

1

0

0

400

100

200

300

500

Time (min)

Control of the cell cycle

Protein kinases- enzymes that can activate or inactivate other proteins by phosphorylating them (Moreno et al. 1989)

control of the cell cycle24
Control of the cell cycle

G1 checkpoint

The sequential events of the cell cycle are directed by a distinct cell cycle control system

  • There are checkpoints where the cell cycle stops until a go-ahead signal is received (cyclin-dependent kinases are involved with these check points)
    • Ie. If the cell does not get the go ahead at the G1 check point, it will enter a non-dividing phase (G0)

Control

system

S

G1

G2

M

M checkpoint

G2 checkpoint

control of the cell cycle25
Control of the cell cycle

G1 checkpoint

The sequential events of the cell cycle are directed by a distinct cell cycle control system

  • There are checkpoints where the cell cycle stops until a go-ahead signal is received (cyclin-dependent kinases are involved with these check points)
    • Ie. If the cell does not get the go ahead at the G1 check point, it will enter a non-dividing phase (G0)
    • Ie. M check point involves the connection of all chromosomes to the spindle (internal control)

Control

system

S

G1

G2

M

M checkpoint

G2 checkpoint

control of the cell cycle26
Control of the cell cycle

Anchorage dependence

External signals

  • Cell may not divide if an essential nutrient is lacking
  • Growth factors (molecules released from other cells or tissues can stimulate division)
  • Density-dependent inhibition-crowded cells stop dividing
  • Anchorage dependence-to divide cells must be attached to a substrate

Density-dependent inhibition

Density-dependent inhibition

25 µm

25 µm

(b) Cancer cells

(a) Normal mammalian cells

control of the cell cycle27
Control of the cell cycle

Anchorage dependence

External signals

  • Cell may not divide if an essential nutrient is lacking
  • Growth factors (molecules released from other cells or tissues can stimulate division)
  • Density-dependent inhibition-crowded cells stop dividing
  • Anchorage dependence-to divide cells must be attached to a substrate

Density-dependent inhibition

Density-dependent inhibition

25 µm

25 µm

(b) Cancer cells

(a) Normal mammalian cells

Cancer cells do not exhibit density-dependent inhibition or anchoring dependence

cancer a loss of control of the cell cycle
Cancer: A loss of control of the cell cycle
  • Cancer cells divide excessively invading other tissues, they can lead to death
  • Why?
    • Some make their own growth factors
    • Some can divide without growth factors
    • They lack density-dependent inhibition and anchorage dependence
cancer a loss of control of the cell cycle29
Cancer: A loss of control of the cell cycle
  • The disease begins with transformation-the process of converting a normal cell to a cancer cell
  • If the transformed cell avoids the immune system it may proliferate and form a tumor
  • A tumor can be benign or malignant (invasive enough to impair other organs)
  • Cells in malignant tumors may have:
    • Unusual chromosome numbers
    • Changes on the cell surface that allow them to spread
    • Cause blood vessels to grow near them
the cell cycle30

You should understand:

  • The importance of cell division
  • The phases of the cell cycle: interphase, mitosis, and cytokinesis
  • Factors that control the cell cycle: molecules involved, checkpoints, internal and external controls
  • Cancer cells have lost control of the cell cycle

The cell cycle