K5- Cell Cycle

8/13/2019 K5- Cell Cycle

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CELLCYCLEBLOKBBS-1

Alya Amila Fitrie

Radita Nur Anggraini GintingMedical SchoolUniversity of Sumatera UtaraMedan 2011


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Where a cell arises, there must be aprevious cell, just as animals can onlyarise from animals and plants from

plants.

Rudolf Virchow (German pathologist) in 1858


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The mammalian cell cycle


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WHATISCELLCYCLE?

A cell reproduces by performing an orderly sequence ofevents in which it duplicatesits contents and thendividesin two.

This cycle of duplication and division, known as theCELL CYCLE, is the essential mechanism by which allliving things reproduce.

DNA must be replicated accurately

The regulation of the cell cycle must ensure that theevents in each phase is complete before moving to thenext check points are important


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WHATISCELLCYCLE?

In multicellular species,long complex sequences

of cell division are

required to produce afunctioning organism.

Even in the adultbody, cell division is

usually needed to

replace cells that die.

In fact, each of us must manufacture many millions

of cells every second simply to survive: if all celldivision were stoppedby exposure to a verylarge dose of x-rays, for examplewe would die

within a few days.


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WHATISCELLCYCLE?

The details of the cellcycle vary from

organism to organism

and at different timesin an organism's life.

Certaincharacteristics,

however, areuniversal.

The minimum set of processes that a cell has toperform are those that allow it to accomplish itsmost fundamental task: the passing on of itsgenetic information to the next generation

of cells.


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INTERPHASE

Interphase generally lasts at least 12 to 24hours in mammalian tissue. During thisperiod, the cell is constantly synthesizingRNA, producing protein and growing in size.

Interphase : divided into 4 steps: Gap 0 (G0),Gap 1 (G1), S (synthesis) phase, Gap 2 (G2).


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GAP0 (G0)

There are times when a cell willleave the cycle and quit dividing.

This may be a temporary restingperiod or more permanent. Anexample of the latter is a cell that

has reached an end stage ofdevelopment and will no longerdivide (e.g. neuron).


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GAP1 (G1)

Cells increase in size in Gap 1, produceRNA and synthesize protein.

An important cell cycle control mechanismactivated during this period (G1Checkpoint) ensures that everything isready for DNA synthesis. (ref: cells alive)


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S- PHASE

To produce two similar

daughter cells, the completeDNA instructions in the cell

must be duplicated. DNA

replication occurs duringthis S (synthesis) phase.


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GAP2 (G2):

During the gap between DNAsynthesis and mitosis, the cell will

continue to grow and producenew proteins. At the end of thisgap is another control checkpoint

(G2 Checkpoint) to determine ifthe cell can now proceed to enterM (mitosis) and divide.


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MITOSISORM PHASE:

Cell growth and protein production stop at this stage.

The cell's energy is focused on the complex andorderly division into two similar daughter cells.

Mitosis is much shorter than interphase, 1-2 hours.

There is a Checkpoint in the middle of mitosis(Metaphase Checkpoint) that ensures the cell isready to complete cell division.


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MITOSIS

Telofase, the two groups of chromosomes reach the opposite ends of the cell.

As a new nuclear envelope starts to form around each group,the chromosomesuncoil and the spindle dissappears

Anafase

the sister chromatids of each chromasome begin to separate

The centromere that holds sister chromatids together devides

and the chromosomes move away from each other along itsspindle fiber

Metafase

the double stranded chromosomes line up along the equator of

the cell

The spinde now fully formed and the microtubules attach to each

sister chromatid

Profase

the chromosomes become visible and condense, becomingshorter and thicker and form sister chromatid

The nuclear envelope breaks dowmn and spindle fibers form asmicrotubules grow out of the centrioles that move to opposite

poles of the cell


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CYTOKINESIS

The divisionof thecytoplasmandorganelles iscalled

cytokinesisor the Cphase

The result ofmitosis andcytokinesis isthe formationof twogenetically

identical cell


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IMPORTANTNOTEFORCELLCYCLE

There is a critical checkpoint in themammalian cell cycle, called RestrictionPoint (R)

Prior to R, the cell depends on externalstimuli (growth factor) to progress throughG1

After R, the cell become independent ofexternal mitogenic stimuli and can complete

the cell division cycle autonomously.


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CELLCYCLEREGULATION

3 principle checkpoints are in G1, G2 and M

G1 (START/restriction point):should DNA be replicated?

G2 : quality control: is DNAreplicated and in good condition?

M: are chromosomes lined upcorrectly?


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CELLCYCLECONTROL

As with most enzyme regulation throughoutthe cell, enzyme control of the cell cycle ismediated in the nucleus through

kinases(enzymes that activate other proteins by theaddition of phosphate groups) and

phosphatases(enzymes that remove phosphate groupsfrom proteins).

The kinases controlling the cell cycle arecalled Cyclin-Dependent Kinases(cdks), so-called because they cannot act without being

conjoined to a cyclinprotein.


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DIFFERENTCYCLIN-CDKDURINGCELLCYCLE

Different cyclins (designated by lettersA,B,D,E) are present in different levelsduring different phases of the cell cycle

The cyclins were named in the order inwhich they were discovered, so there isno logical relation between the letterand the cell cycle phase.

Similarly, the cdk enzymes aredesignated by number (cdk4, cdk2,cdk1) according to when they werediscovered.


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CYCLIN

Cyclins are named cyclins because theirappearance during the cell cycle is cyclical.

The 1stcyclin synthesis in response togrowth factor stimulatory signal is cyclin D

Mid G1, cyclin E followed by cyclin A at G1to S transtition. Cyclin B at G2 and Mphase.

The periodicity of cyclin is mediated bytheir synthesis and subsequent proteolysisdegradation by ubiquitin/proteasomeswhen their services are no longer required.


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WHYARETHERELATIONBETWEENCANCER

ANDCELLCYCLE?

Cancer, result from multiple genetic alteration ingenes that control: proliferation

differentiation

programmed cell death (apoptosis) Many genes that are mutated in human cancer,

directly involved in regulation of the cell divisioncycle, they are linked to the machinery that controlscell proliferation.

Two groups of cancer genes oncogenes, mutated version of genes, normal function is to

stimulate cell proliferation

tumor suppressor genes, normally restrict growth


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Summary


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