Cell cycle

M. K. TadjudinFakultas Kedokteran dan Ilmu

KesehatanUniversitas Islam Negeri

Syarif HidayatullahJakarta

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Phases in the cell cycle

•G1 = growth and preparation of the chromosomes for replication

•S = synthesis of DNA and centrosomes

•G2 = preparation for mitosis

•M = mitosis

INTERPHASE

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Proteins controlling cell cycle

• Cyclins – a G1 cyclin (cyclin D) – S-phase cyclins (cyclins E and A) – mitotic cyclins (cyclins B and A)

• Cyclin-dependent kinases (Cdks) – a G1 Cdk (Cdk4) – an S-phase Cdk ((Cdk2) – an M-phase Cdk (Cdk1)

• Anaphase-promoting complex (APC). (The APC is also called the cyclosome, and the complex is often designated as the APC/C.) The APC/C – triggers the events leading to destruction of the cohesins

thus allowing the sister chromatids to separate; – degrades the mitotic cyclin B

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Steps in the cell cycle (1)

• A rising level of G1-cyclins bind to their Cdks and signal the cell to prepare the chromosomes for replication

• A rising level of S-phase promoting factor (SPF) — which includes cyclin A bound to Cdk2 — enters the nucleus and prepares the cell to duplicate its DNA (and its centrosomes)

• As DNA replication continues, cyclin E is destroyed, and the level of mitotic cyclins begins to rise (in G2)

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Steps in the cell cycle (2)

• M-phase promoting factor (the complex of mitotic cyclins with the M-phase Cdk) initiates – assembly of the mitotic spindle – breakdown of the nuclear envelope – condensation of the chromosomes

• These events take the cell to metaphase of mitosis.

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Steps in the cell cycle (3)

• These events take the cell to metaphase of mitosis.

• At this point, the M-phase promoting factor activates the anaphase-promoting complex (APC/C) which – allows the sister chromatids at the metaphase

plate to separate and move to the poles (= anaphase), completing mitosis

– destroys cyclin B. It does this by attaching it to the protein ubiquitin which targets it for destruction by proteasomes

– turns on synthesis of G1 cyclin for the next turn of the cycle

– degrades geminin, a protein that has kept the freshly-synthesized DNA in S phase from being re-replicated before mitosis

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Mitosis1. Prophase2. Prometaphase3. Metaphase4. Anaphase5. Telophase

Cytokinesis

Nucleus

Cytoplasm

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Interphase (1)• The cell is engaged in metabolic

activity and performing its prepare for mitosis (the next four phases that lead up to and include nuclear division)

• Chromosomes are not clearly discerned in the nucleus, although a dark spot called the nucleolus may be visible

• The cell may contain a pair of centrioles (or microtubule organizing centers in plants) both of which are organizational sites for microtubules

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Interphase (2)

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Prophase (1)• The two centrosomes of the cell, each

with its pair of centrioles, move to opposite "poles" of the cell.

• The mitotic spindle forms. This is an array of spindle fibers, each containing ~20 microtubules. Microtubules are synthesized from tubulin monomers in the cytoplasm and grow out from each centrosome.

• The chromosomes become shorter and more compact.

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Prophase (2)

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Prometaphase (1)

• The nuclear envelope disintegrates because of the dissolution of the lamins that stabilize its inner membrane.

• A protein structure, the kinetochore, appears at the centromere of each chromatid.

• With the breakdown of the nuclear envelope, spindle fibers attach to the kinetochores as well as to the arms of the chromosomes.

• For each dyad, one of the kinetochores is attached to one pole, the second (or sister) chromatid to the opposite pole. Failure of a kinetochore to become attached to a spindle fiber interrupts the process.

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Prometaphase (2)

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Metaphase (1)

•At metaphase all the dyads have reached an equilibrium position midway between the poles called the metaphase plate

•The chromosomes are at their most compact at this time

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Metaphase (2)

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Metaphase (3)

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Mechanisms of spindle movements

1. Microtubules attached to opposite sides of the dyad shrink or grow until they are of equal length.

2. Microtubules motors attached to the kinetochores move them 1.toward the minus end of shrinking

microtubules (a dynein); 2.toward the plus end of lengthening

microtubules (a kinesin).

3. The chromosome arms use a different kinesin to move to the metaphase plate

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Anaphase (1)• The sister kinetochores suddenly separate and

each moves to its respective pole dragging its attached chromatid (chromosome) behind it

• Separation of the sister chromatids depends on the breakdown of the cohesins that have been holding them together

• Cohesin breakdown is caused by a protease called separase (also known as separin).

• Separase is kept inactive until late metaphase by an inhibitory chaperone called securin.

• Anaphase begins when the anaphase promoting complex (APC) destroys securin (by tagging it for deposit in a proteasome) thus ending its inhibition of separase and allowing separase to break down the cohesins

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Anaphase (2)

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Telophase (1)

•A nuclear envelope reforms around each cluster of chromosomes and these return to their more extended form

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Telophase (2)

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Cytokinesis (1)• Separation of a cell into two• In animal cells, a belt of actin filaments forms

around the perimeter of the cell, midway between the poles. The interaction of actin and a myosin (not the one found in skeletal muscle) tightens the belt, and the cell is pinched into two daughter cells

• In plant cells, a membrane-bounded cell plate forms where the metaphase plate had been. The cell plate, which is synthesized by the Golgi apparatus, supplies the plasma membrane that will separate the two daughter cells. Synthesis of a new cell wall between the daughter cells also occurs at the cell plate

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Cytokinesis (2)

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Meiosis• Two consecutive divisions:

meiosis I and meiosis II • No DNA synthesis (no S phase)

between the two divisions • The result: 4 cells with half the

number of chromosomes of the starting cell, e.g., 2n → n

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Phases of meiosis

• Meiosis I– Prophase I– Metaphase I– Anaphase I

• Meiosis II– Chromosome behavior in meiosis II is like that of

mitosis

– At metaphase II, spindle fibers attach one kinetochore of the dyad to one pole, the other to

the opposite pole then the chromatids separate and (each now an independent chromosome)

move to their respective poles

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Prophase I (1)1.Leptotene

Condensation and pairing of chromosomes

2.Zygotene Synaps Start of recombination

32Synapsis

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Prophase I (2)3.Pachytene

Synapsis complete Recombination nodules

appear Chromosome appears

thick

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Prophase I (3)4.Diplotene

DNA recombination is complete The synaptonemal complex begins

to break down The chromatids begin to pull apart

revealing chiasmata. At first the chiasmata are located

at the sites of the recombination nodules, but later they migrate towards the ends of the chromatids

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Prophase I (4)5.Diakinesis

In some organisms, the chromosomes decondense and begin to be transcribed for a time. This is followed by the chromosomes recondensing in preparation for metaphase I

In creatures where this does not occur, the chromosomes condense further in preparation for metaphase I

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39Metaphase I: Crossing over and recombination (1)

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Metaphase I: Crossing over and recombination (2)

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Recmbination in Neurospora

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Random assortment

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Bibliography• Kellogg, E. A. and N. D. Juliano. 1997. The structure

and function of RuBisCO and their implications for systematic studies. American Journal of Botany 84:413-428.

• Langridge, J. 1991. Molecular genetics and comparative evolution. John Wiley & Sons, Inc., New York, New York. 216 pp.

• Raven, P. H., R. F. Evert, and S. E. Eichhorn. 1992. Biology of plants, 5th ed. Worth Publishers, New York, New York. 791 pp.

• Suzuki, D. T., A. J. F. Griffiths, J. H. Miller, and R. C. Lewontin. 1989. An introduction to genetic analysis, 4th ed. W. H. Freeman and Company, New York, New York. 768 pp.

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