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THE CELL CYCLE

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THE CELL CYCLE

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CELL DIVISION

A characteristic of living organisms is the ability to reproduce—this occurs through cell division.

Cell division can result in…

• a new organism (in the case of unicellular organisms)

• a multicellular organism that develops from a single cell.

• the renewal and repair of damaged or older cells.

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CELL DIVISION

• Cell division is just one part of the cell cycle. The cell cycle is the entire life of a cell from when it forms to when it divides.

• For cell division to be successful, genetic material must be copied with fidelity and the entire

genome as well as organelles must be distributed to two daughter cells.

• Organisms that reproduce sexually have two

types of cells—somatic cells and reproductive

cells (gametes). Somatic cells have twice as

many chromosomes as gametes do.

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CHROMOSOME STRUCTURE

• Once duplication of genetic material has occurred, each chromosome has two sister chromatids.

• These contain identical genetic material and are attached to each other by protein complexes known as cohesins (the attachment is known as sister chromatid cohesion).

• The Kinetochore is a structure of proteins associated with specific

sections of DNA. These are found in the centromere and help with

movement of chromosomes

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THE CELL CYCLE

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THE CELL CYCLE

The cell cycle has two main phases:

1) The mitotic phase (M) takes up about 10% of the cycle.

2) Interphase (G

1

, S, and G

2

) takes up about 90% of

the cell cycle.

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MITOSIS

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G2 OF INTERPHASE

• Nucleus fully intact with nuclear membrane.

• Two centrosomes present (will contain centrioles in animal cells).

• Chromosomes not visible.

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PROPHASE

• Chromatin condenses.

• Mitotic spindle begins to form.

• Centrosomes migrate.

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PROMETAPHASE

• Nuclear membrane begins to disassemble.

• Chromatin continues to condense.

• Each chromatid has a kinetochore.

• Some microtubules attach to kinetochores.

• Nonkinetochore microtubules interact with each

other.

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METAPHASE

• Longest step (lasts app 20 minutes).

• Centrosomes at opposite poles.

• Chromosomes line up at metaphase plate.

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ANAPHASE

• Shortest step.

• Cohesion proteins are cleaved. Chromatids are now referred to as chromosomes.

• Chromosomes move to opposite poles (at about 1 mm/min).

• Cell elongates.

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TELOPHASE

• Two daughter nuclei form.

• Chromosomes unravel.

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CYTOKINESIS

• Cleavage furrow forms. This is created by

contractile ring of actin microfilaments associated with myosin.

• In plant cells, a cell plate forms from vesicles

derived from the Golgi apparatus (these also

contain material for building new cell wall).

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THE MITOTIC SPINDLE

• The mitotic spindle begins to form during prophase.

• It is made of microtubules and associated proteins.

• It grows in length by adding subunits of tubulin.

• Mitotic spindles start at centrosomes.

Centrosomes replicate during interphase and

migrate to opposite poles during prophase and

prometaphase.

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BINARY FISSION VS MITOSIS

• In prokaryotic cells, chromosome begins to replicate at origin of

replication. As chromosome is copied, one version of DNA

migrates to opposite pole of cell.

• While this is occurring, the cell is also elongating.

• When replication of DNA is complete AND cell is

approximately twice its original

length, division of cell occurs.

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CELL CYCLE CONTROL SYSTEMS

The cell cycle control system…

• is a cyclically operating set of molecules in the

cell that both trigger and coordinate key events in the cell cycle.

• Involves checkpoints which contain signals that tell the cell to proceed with the cell cycle or enter a period of stasis. These signals are transmitted by signal transduction pathways. STOP is the

default mode of the cell. A cell must receive a signal to proceed.

• Has checkpoints at G

1

, G

2

, and M.

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CELL CYCLE CONTROL POINTS

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CELL CYCLE CONTROL POINTS

• G

1

is seemingly the most important checkpoint.

Because of this, it is also referred to as the restriction checkpoint.

• If a cell goes through the G

1

checkpoint, it usually continues on through S, G

2

and M phases. If it

does not receive the signal during the G1

checkpoint, it enters a non-dividing state known

as G

O

.

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CELL CYCLE CONTROL

• Cell cycle control molecules (which are mostly proteins) pace the events of the cell cycle.

• Protein Kinases: enzymes that activate (or inactivate) other proteins by phosphorylating them. Many protein kinases are present at a

relatively constant level; however, they are in an inactive form. These kinases can be activated by having a protein known as a cyclin attached to it.

These are known as cyclin-dependent kinases (Cdks).

• The Cdks activity cycles with its cyclin partner.

Cyclin production is controlled by growth factors.

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CELL CYCLE CONTROL: AN EXAMPLE

• Maturation-promoting factor (MPF) is a cyclin-Cdk complex that triggers the cell to move past G

2

checkpoint.

• Cyclins associated with this complex rise during S and G

2

phases, binding with MPF complex and activating it.

• MPF complex then phosphorylates a variety of

proteins which serve to initiate mitosis. Some proteins exist in the nuclear lamina and they stimulate break down of nuclear envelope. Others may contribute to condensation of chromosomes and spindle production.

• MPF also sets in motion a series of reactions that

actually degrades its own cyclin.

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CELL CYCLE CONTROL

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REGULATION OF THE CELL CYCLE: CYCLINS AND CYCLIN DEPENDENT KINASES (CDKS)

During G1, conditions in the cell favor degradation of cyclin, and the Cdk

component of MPF is

recycled.

5

4. During anaphase,

cyclin of MPF is degraded.

Stops M phase. Cell enters G1.

Accumulated cyclin combines with Cdk, producing enough MPF to pass the G2 checkpoint initiating mitosis.

2

Synthesis of cyclin in late S, and

through G2. Cyclin is protected from

degradation now and accumulates.

1

Cdk

G2 Cdk checkpoint

Cyclin MPF

Cyclin is degraded Degraded Cyclin

G1

G2 S M

G1

G1 S G2 M S G2 M

MPF activity Cyclin

Time (a) Fluctuation of MPF activity and

cyclin concentration during the cell cycle

MPF phosphorylates various proteins initiating Mitosis

3 M

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CELL CYCLE CONTROL:

INTERNAL AND EXTERNAL SIGNALS

M checkpoint:

• When the kinetochores of all the chromosomes in a cell are attached to a spindle fiber, a regulatory protein is activated.

• This protein sets off a chain of reactions that

eventually forms enzymes which cleave cohesins.

G

1

checkpoint control:

• External molecules, such as growth factors, can bind to receptor kinases and trigger a signal

transduction pathway allowing cells to pass G

1

checkpoint.

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CELL CYCLE CONTROL: EXTERNAL FACTORS

• Density-dependent inhibition occurs in cells that stop dividing in crowded conditions. When cells are in physical contact, binding of cell-surface proteins sends a growth-inhibiting signal to both cells.

• Anchorage dependence occurs in other cells. In

this type of cell, the cell must be attached to a

substrate to divide.

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