Cell Reproduction:

Mitosis and Meiosis

Theme - Continuity and diversity

Terms • Anaphase• Aster• Benign tumor• Binary fission• Cell cycle• Cell division• Cell plate• Centromere• Checkpoint

• Chromatin

• Chromosome

• Cleavage

• Cleavage furrow

• Cyclin

• Cyclin-dependent kinase (Cdk)

• Cytokinesis

• Density dependent inhibition

• G0

• G1

• G2

• Gamete

• Genome

• Growth factors

• Interphase

• Kinetochore

• M phase

• Malignant tumor

• Meiosis

• Metaphase

• Mitosis

• MPF

• Origin of replication

• Prophase

• S phase

• Sister chromatids

• Somatic cell

• Telophase

• Transformation

Contrast

• Mitosis • 2, diploid, identical

cells• Growth, repair,

replace, asexual reproduction

• Meiosis • 4, haploid, non-identical

cells• Sexual reproduction

• Genome – cell’s genetic information

– Prokaryote = single long, circular DNA (?)• E. coli – 3200 genes

• H. influenzae – 1700 genes

• Bacteria divide by binary fission

– Eukaryote = several DNA molecules

Chromosomes

Chromosomes

• Genes - sections of DNA with code for making proteins– Humans = 25,000* Humans = 25,000*

(est. HGP)(est. HGP)– 3.2 bbp3.2 bbp– Mice - 2.6 bbp(40 chromosomes)Mice - 2.6 bbp(40 chromosomes)– Average gene - 3000 nucleotides Average gene - 3000 nucleotides

• DNA is making proteins most of the time

• Chromatin = DNA + histones (proteins)– Stabilize and enable DNA

to work• After replication, chromatin

condenses, coils and folds into a chromosome

DNA = Chromatin

Chromosome # 19

Chromosomes Chromosomes

• Each chromosome = two sister chromatidschromatids

• CentromereCentromere = connects the two chromatidschromatids

• Sister chromatids are pulled apart and repackaged into two new nuclei at opposite ends of the parent cell

Chromosomes• Each species has a characteristic number of

chromosomeschromosomes– Human somatic cellssomatic cells have

46 (diploid)– Human gametesgametes have 23

(haploid)• KaryotypeKaryotype – arrangement of

chromosomes – Picture taken during

metaphase

Karyotype – arrangement of chromosomes according to…

• Cell cycle – sequence of events in the life of a cell

• Two periods:

– Interphase

– Mitosis

Cell Cycle Cell Cycle

• Interphase - cell growth

– Longest time of the cycle

– Three subphases:

• G1 (“first gap”) growth

• S (“synthesis”) DNA is copied

• GG22 (“second gap”) cell completes preparations for division

• GG00 – some cells do not re-enter ‘S’

Cell CycleCell Cycle

Cell Cycle

• M phase

– Mitosis – division of the ___ and _____

– Cytokinesis – division of the _________

• Produces two cells genetically identical cells

• Asexual reproduction – one parent

• Mitosis is a continuum:

– Mitosis is ‘usually’ broken into five subphases:

• Prophase

• Prometaphase

• Metaphase

• Anaphase

• Telophase

• Late interphase, DNA has been replicated but is not packed/coiled

• The centrosomes have been duplicated and begin to organize microtubules into an aster (“star”)

Cell Cycle

• Prophase - the chromosomes are tightly coiled, with sister chromatids joined together by a centromere

• The nucleoli disappear

• The mitotic spindle begins to form and appears to push the centrosomes apart

• Prometaphase – Nuclear envelope fragments

and microtubules from the spindle interact with the chromosomes

– Kinetochores – special regions of the spindle, attach to the centromere

• Metaphase - spindle fibers push the sister chromatids until they are all arranged at the metaphase plate

• Anaphase - centromeres divide, separating sister chromatids

• Each chromatid is pulled toward the pole to which it is attached by spindle fibers

• Telophase - cell continues to elongate

– Free spindle fibers from each centrosome push against each other

• Two nuclei envelopes begin to reform

• Chromatin uncoils

• Cytokinesis begins

• SpindleSpindle (microtubules)microtubules) drives mitosis

• SpindleSpindle forms during prophase

– Parts come from partial disassembly of cytoskeletoncytoskeleton

• Spindle elongates by adding more tubulin (protein)

Spindle Distributes Chromosomes to Daughter Cells

• Assembly of spindle starts in the centrosome.

• MTOC (microtubule-organizing center)

– Animal cells have a pair of centrioles at the center, function is unclear

Spindle Distributes Chromosomes

• As mitosis starts, the two centrosomes are located near the nucleus

• As the spindle fibers, the centrioles are pushed apart

• By the end of prometaphase they develop as the spindle poles at opposite ends

Spindle Distributes Chromosomes

• Each sister chromatid has a kinetochore (proteins and chromosomal DNA) at the centromere

• During prometaphase, some spindle microtubules attach to the kinetochores

Spindle

• Nonkinetichore microtubules lengthen the cell

– Microtubules interdigitate across the metaphase plate

– During anaphase, motor proteins push microtubules from opposite sides away from each other

– New tubulin monomers extends the length

• Animal cells:

• Cleavage furrow - contractile ring of actin and myosin form

• Contraction of the ring pinches the cell in two

Cytokinesis Divides Cytoplasm

• Plants, have cell walls

• Cell plate - vesicles from Golgi coalesce at the metaphase plate

– Plate enlarges until fused with the plasma membrane

Cytokinesis Divides Cytoplasm

Fig. 12.9

• Prokaryotes reproduce by binary fissionbinary fission

• Most genes on one chromosome; (circular DNA + proteins)

• Not as many genes or as much DNA as eukaryotes

Mitosis May Have Evolved From Binary Fission in Bacteria

• Replication begins at the Origin of Replication

• Chromosome replicates

• Bacterium doubles in size

• Plasma membrane grows inward

• Pinches parent cell into two daughter cells

Binary Fission in Bacteria

• Big jump from binary fission to mitosis.

• Possible intermediate evolutionary steps are seen in the division of two types of unicellular algae.

– In dinoflagellates, replicated chromosomes are attached to the nuclear envelope.

– In diatoms, the spindle develops within the nucleus.

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Fig. 12.11

CHAPTER 12 THE CELL CYCLE

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Section C: Regulation of the Cell Cycle

1. A molecular control system drives the cell cycle

2. Internal and external cues help regulate the cell cycle

3. Cancer cells have escaped from cell cycle controls

• Timing and rates of cell division in different parts are crucial for growth, development, and maintenance.

• Frequency of cell division varies with cell type.

– Skin cells divide frequently

– Liver cells do not divide unless damaged

– Nerve and muscle cells do not appear to divide after maturity.

• Investigation of molecular mechanisms regulating cell division helps determine normal cell division

• Knowing normal cell helps determine CancerCancer

• Cell cycle appears to be driven by chemical signals in the cytoplasm

– Ex.• Fusion of an S phase and a G1 phase cell, induces

the G1 nucleus to start S phase.• Fusion of a cell in mitosis with one in interphase

induces the second cell to enter mitosis.

A Molecular Control System Drives the Cell Cycle

Cell Cycle Control

• Checkpoint in cycle is a control point

– ChemicalChemical stop stop andand gogo ssignals

– Checks to be sure all steps are completed

– Chemical signals from outside (hormones) are also controls

• 3 checkpoints; G1, G2, and M phases

Cell Cycle Control

• G1 checkpoint (restriction point) is most important– Go signal = completes cell cycle and divides– No go = cell exits cycle;

• Switches to non-dividing state, GG00 phase phase (most human cells; liver, nerve, muscle)

Cell Cycle Control

• Rhythmic fluctuations of proteins control the cycle

– KinasesKinases - activate or deactivate other proteins • Constant amount

– Cyclins – levels fluctuate

• Kinases and cyclin forms cyclin-dependent cyclin-dependent kinases (Cdks)kinases (Cdks)

• CyclinCyclin levels rise during interphase, then fall during mitosis

• MPF – type of cyclin-Cdk complex– “maturation-promoting factor” triggers cell past G2

checkpoint to M phase– Stimulates fragmentation of

the nuclear envelope

– Inactivates MPF

Cell Cycle Control

Internal and External Cues

• M phase checkpoint ensures that the chromosomes are attached to the spindle at metaphase plate before anaphase begins

– Daughter cells do not end up with missing or extra chromosomes

• Chemical signal comes from kinetochores that have not yet attached to spindle

– Anaphase-promoting complex (APC) remains inactive

– When kinetochores are attached, APC activates

• Breaks down cyclin

• Inactivates centromere proteins

Internal and External Cues

• Growth factorsGrowth factors (protein hormones) released by some cells; stimulate other cells to divide

• Ex. injury

– Platelet-derived growth factors (PDGF), produced by platelet blood cells, bind to receptors on fibroblasts (connective tissue)

– Triggers cell division

– Wound heals

Internal and External Cues

• Role of PDGFPDGF determined in cell cultures:– Fibroblasts in culture will only divide with

PDGF

Internal and External CuesScience As A ProcessScience As A Process

• DensityDensity-dependent dependent inhibitioninhibition – Cultured cells normally

divide until they form a single layer

– Cells will grow to fill a gap– At high densities, not

enough growth factor and nutrient for all cells

Internal and External Cues

• AnchorageAnchorage dependencedependence – Must be anchored to

a substrate (extracellular matrix of tissue)

• Cancer cellsCancer cells do not respond to density-dependent inhibition or anchorage dependence.

Internal and External Cues

• Cancer cells do not stop dividing when growth factors are depleted

– Manufacture their own growth factors (?)

– Abnormality in the signaling pathway

– Problem in the cell cycle control system

• If cells stop dividing it is at random, not the normal checkpoints

Cancer Cells Not Under Cell Cycle Controls

• Cancer cells may divide indefinitely if they have a continual supply of nutrients

• Normal cells divide 20 to 50 times (in vitro) before they stop, age, and die

– Cancer cells may be “immortal”• Cells (HeLa) from a tumor removed from a

woman (Henrietta Lacks) in 1951 are still reproducing in culture.

Cancer

Cancer• A cell in a tissue undergoes a transformation

converts it from normal to cancer– Normally, immune system recognizes and

destroys transformed cells– Some cells escape destruction and

reproduce to form a tumor tumor (lump)(lump)

Cancer Tumors

• Two types: benign, malignant• BenignBenign – tumor remains at original site –

surgery• MalignantMalignant – cell leave original site, spread

to other organs• MetastasisMetastasis – tumor cells pop ‘loose’ enter

lymph

Cancer - Treatment

• Surgery

• Radiation and chemotherapy

• Interrupt cell cycle

– Mitotic spindle

– Block Cdk’s

– Lose other dividing cells; skin

The next few slides are The next few slides are of various skin cancers, of various skin cancers, the most common type the most common type of cancer. You do not of cancer. You do not have to look……have to look……

Squamal cell carcinoma

WARNING: the WARNING: the following picture may following picture may cause you to lose your cause you to lose your

lunch….lunch….

Normal border IrregularIrregular borderborder

Malignant melanomas

‘Tags’: benign tumor

Seborrheic Keratosis: benign melanocyte

‘tumor’