chapter 12 mitosis and the cell cycle - parkway schools ... 12 notes.pdf · task – diagramming...

Chapter 12Mitosis and the Cell Cycle

A. BergeronAP BiologyPCHS

Task – Diagramming the Cell Cycle

1. You will be assigned one stage of the cell cycle.

2. Your task is to draw an illustration of this stage (without looking at your textbook) and to list as many of the key events that take place during this stage as you can.

3. When you are finished, find other individuals in the class who have a different stage of the cell cycle. Try to organize your white boards into a chronological depiction of the cell cycle based upon the illustrations and the descriptions.

4. The first group to successfully organize their boards into a coherent and accurate representation of the cell cycle will earn three (3) extra credit points on the next test. The second group will earn two (2) points. The third group will earn one (1) point.

? ? ?

Do Now – Understanding Cellular Reproduction

Why Do Cells Need to Reproduce?

List 3 reasons why a cell might need to divide.


Growth (of an

organism)

Replacement(of old or

dying cells)

Repair (of damaged

cells)

Example: Organisms Grow When Cells Divide!Development of a Worm

Animal Cell Division

Sea Urchin Development

• In unicellular organisms, division of one cell reproduces the entire organism

• Multicellular organisms depend on cell division for:– Development from a fertilized cell– Growth– Repair

• Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division


What is Overall Goal of Cell Reproduction???

DNA copied

One copy of DNA

passed on to next

generation

of cells

One copy of DNA passed on to next

generationof cells

“DNA Coiling” - Formation of a ChromosomeCellular DNA (chromatin) is composed of both DNA & protein! -Approximately 40% DNA and 60% protein

A single DNA molecule (chromosome) is made up from 140million nucleotides (depending on size of chromosome)! -”Stretched out” a single chromosome of this size would ! measure close to 5 centimeters in length! -In a typical human cell, 9 meters of DNA are packaged! within the nucleus

How does all of this DNA “fit” inside the nucleus?

“DNA Packaging” - Formation of a Chromosome

NucleosomeComposed of positively charged histone proteinsthat interact with negativelycharged DNA molecules

≈150 DNA base pairs “wrap” around each histone complex (approx. 2.5 turns)

What is the charge on DNA?

Chromatin Packaging

Chromatin Packaging

Nucleosome

Fiber

Loops

Rosettes

Structure of a Chromosome• Chromosomes are only

visible when a cell is getting ready to divide

• Chromatin (combination of DNA and protein) is packaged into chromosomes before mitosis begins

• Chromosomes have the typical “X” shape only after they have been copied and packaged

• Each half of the “X” is called a sister chromatid

• The two sister chromatids are attached by a structure called the centromere

Sister chromatid

Centromere

Chromosomes from a Cell Preparing to Divide

Chromosomeduplication(including DNAsynthesis)

0.5 µm

Centromere

Sisterchromatids

Separationof sister

chromatids

Centromeres Sister chromatids

What is the Overall Goal of Cell Reproduction???

An “exact” copy of the parent cell’s DNA is passed on to subsequent generations of cells

• Eukaryotic cell division consists of:– Mitosis, the division of the nucleus– Cytokinesis, the division of the cytoplasm

• Gametes are produced by a variation of cell division called meiosis

• Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell

Mitosis vs. Meiosis

• The cell cycle consists of– Mitotic (M) phase (mitosis and cytokinesis)– Interphase (cell growth and copying of chromosomes in

preparation for cell division)

• Interphase (about 90% of the cell cycle) can be divided into subphases:

– G1 phase (“first gap”)

– S phase (“synthesis”)

– G2 phase (“second gap”)

The Cell Cycle

G1

G2

S(DNA synthesis)

INTERPHASE

Cytokinesis

MITOTIC(M) PHASE

Mitosis

A Typical Eukaryotic Cell Cycle

G0

R.P. G1 --> S

C.P. G2--> M

C.P. S--> G2

• Stage of the cell cycle where a cell spends 90% of its life

• The cell prepares for cell division during interphase– The cell makes new

molecules and organelles• Interphase can be divided into

3 “mini-stages” ! G1 (Gap/Growth 1) - Cell

grows, organelles replicated,! period of rapid protein

synthesis!! S (Synthesis) - DNA copied! G2 (Gap 2) - Cell finishes

growing and prepares to divide• G0 - A period of cell stasis

– Cell is not preparing to divide

Interphase

Interphase Animation

Mitotic Phase• Composed of two parts

1) Mitosis (Prophase, Prometaphase, Metaphase, Anaphase, and Telophase)• DNA within the nucleus

is evenly distributed into two new daughter cells

2) Cytokinesis• Cytoplasm is distributed

into two new daughter cells during/ immediately after telophase

Mitosis Overview

The “Mitosis Dance”

Mitosis - All PhasesMitosis Animation

G2 OF INTERPHASE PROPHASE PROMETAPHASE

Mitosis Images

METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS

10 µ

m

Mitosis Images - Animal Cells

Animal Cell MitosisChromatin condenses into chromosomesNuclear membrane disintegratesNucleolus breaks apart and disappearsNuclear spindle begins to form(organized at centrioles)Chromosomes attach to kinetochore microtubules

Chromosomes align in middle of cell along metaphase plate (imaginary structure)Spindle completely formed

Prophase Animation

Prometaphase Animation

Metaphase Animation

Animal Cell Mitosis

Chromosomes separate at centromereSister chromatids “pulled” to opposite ends of cell (via motor proteins present at kinetochore)

Nuclear membranes re-formChromosomes de-condense“Reverse’ of prophaseCytokinesis begins via the formationof a cleavage furrow btw 2 new cells


Anaphase Animation

Telophase Animation

Cytokinesis Animation

Plant Cell MitosisDNA replicatedNucleoli visibleChromosomes not visible --> DNA in theform of chromatin

Same as in animal cells


Plant Cell MitosisSame as in animal cells

Same as in animal cells


Plant Cell MitosisSimilar to animal cellsFormation of cell plate during cytokinesis


Interphase and the Mitotic Phase of theCell Cycle Animation

http://www.biology.arizona.edu/cell_bio/tutorials/cell_cycle/cells3.htmlAnother Mitosis Animation

Mitosis Quicktime Movie (w/ text annotation)http://www.sci.sdsu.edu/multimedia/mitosis/mitosis_qt1.html


Animal Cell vs. Plant Cell CytokinesisFormation of cleavage furrow in animal cells! Contractile ring of microtubules pinches cell in half! creating two new cellsFormation of cell plate in plant cells! Vesicles transport cell wall and cell membrane ! materials to middle of cell

• In animal cells, cytokinesis occurs by a process known

as cleavage, forming a

cleavage furrow

Cytokinesis - A Closer Look (Animals)

Cleavage furrow100 µm

Contractile ring ofmicrofilaments

Daughter cells

Cleavage of an animal cell (SEM)

1 µm

Daughter cellsCell plate formation in a plant cell (TEM)

New cell wallCell plate

Wall ofparent cell

Vesiclesformingcell plate

Cytokinesis - A Closer Look (Plants)In plant cells, a cell plate forms during cytokinesis

• The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis

• Assembly of spindle microtubules begins in the centrosome, the microtubule organizing center

• The centrosome replicates, forming two centrosomes that migrate to opposite ends of the cell, as spindle microtubules grow out from them

• An aster (a radial array of short microtubules) extends from each centrosome

The Mitotic Spindle – A Closer Look

• The spindle includes the centrosomes, the spindle microtubules, and the asters

• Some spindle microtubules attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate

• Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell

• In telophase, genetically identical daughter nuclei form at opposite ends of the cell



Do Now – Chromosome Calculations1. At which stage/s of the cell cycle do human skin cell nuclei have the same DNA content?

a. Early prophase and late telophaseb. G1 and G2c. G1 and early prophased. G1 and late telophasee. G2 and late telophase

2. A cell has 16 chromosomes. How many chromosomes will be present in a cell at the following stages of the cell cycle?

a. G1 d. Anaphaseb. G2 e. Prophasec. Metaphase

Hint: Chromosomes are visible structures composed of DNA and protein


Microtubules Chromosomes

Sisterchromatids

AsterCentrosome

Metaphaseplate

Kineto-chores

Kinetochoremicrotubules

0.5 µm

Overlappingnonkinetochoremicrotubules

1 µmCentrosome

• Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell

• In telophase, genetically identical daughter nuclei form at opposite ends of the cell


• In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell

• The microtubules shorten by depolymerizing at their kinetochore ends


Chromosomemovement

Microtubule Motorprotein

Chromosome

Kinetochore

Tubulinsubunits

Dyenin Moves Chromosomes During Mitosis

1) Spindle microtubules slide past each other carrying the chromosomes with them.

Two hypotheses for chromosomal translocation during mitosis

2) Spindle microtubules shorten at the centromere and the chromosomes move using a specialized motor protein.


Blue stain = DNAGreen = TubulinRed = Dynein

Remember chromosome structureduring mitosis:

1. Chromatin has condensed into chromosomes

2. Sister chromatids are attached at the centromere

3. Kinetochore has attached duplicated chromosomes to the spindle


Green = DNARed = Tubulin

p50 = Dyenininhibitor

What Do Animal Cells Going Through Stages of the Cell Cycle Look Like?

NucleusCell plateChromosomesNucleolus

Chromatincondensing 10 µm

Prophase. The chromatin is condensing.The nucleolus is beginning to disappear.Although not yet visible in the micrograph, the mitotic spindle is starting to form.

Prometaphase. Wenow see discrete chromosomes; each consists of two identical sister chromatids. Laterin prometaphase, the nuclear envelope will fragment.

Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate.

Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of the cell as their kinetochore microtubules shorten.

Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divide the cytoplasm in two, is growing toward the perimeter of the parent cell.

What Do Plant Cells Going Through Stages of the Cell Cycle Look Like?

Root Tip (Plant) Mitosis

Identifying Stages of the Cell CycleChapter 8 Review (University of Arizona)

What Do Plant Cells Going Through Stages of the Cell Cycle Look Like?

• Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission

• In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart

Cell Reproduction in Prokaryotes - Binary Fission

Origin ofreplication

Cell wall

Plasmamembrane

Bacterialchromosome

E. coli cell

Two copiesof origin

Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell.

Replication continues. One copy of the origin is now at each end of the cell.

Origin Origin

Replication finishes. The plasma membrane grows inward, and new cell wall is deposited.

Two daughtercells result.

Cell Reproduction in Prokaryotes - Binary Fission

Cell Reproduction in Prokaryotes - Binary FissionBacteria possess a single circular chromosome made of DNA and proteinChromosome replicatedprior to cell divisionCopy of each chromosomedistributed into each newcell as cell membrane pinches and a new cell wall forms between the two cells

• The frequency of cell division varies with the type of cell• These cell cycle differences result from regulation at the

molecular level

Which Factors Control the Cell Cycle?

• The cell cycle appears to be driven by specific chemical signals present in the cytoplasm

• Some evidence for this hypothesis comes from experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei

What Are These Chemical Signals?

Do Now – Cancer BiologyTumor formation is governed by improper cell cycle signalingwhich is brought about by a dysregulation of intracellualar andextracellular signaling events.

The presence of MPF (i.e. a cyclin/cdk complex) is required for a cell to move from G2 into mitosis

Using this signaling event as a starting point, briefly describe how a cell could be stimulated to divide in an uncontrolled manner. Consider the following as you formulate your answer:

1. What is the role of checkpoints in uncontrolled cell division?2. What are the role of proto-oncogenes and tumor suppressor genes in cell division?3. How is DNA mutation involved in the deregulation of cell division?

Do Now – Making Predictions

1. Predict what would happen if a cell in the S phase was fused to a cell in the G1 phase. Explain.

2. Predict what would happen if a cell in mitosis were fused to a cell in the G1 phase. Explain.

3. Predict what would happen if a cell in G1 were fused to a cell in G2. Explain.

Experiment 1 Experiment 2

S

S S

G1 G1M

M M

When a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized.

When a cell in the M phase was fused with a cell in G1, the G1 cell immediately beganmitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.

Ubiquitin-targeted Destruction of Cellular ProteinsTranslation can be controlled by regulating whether or not theribosomal subunits are able to bind to the mRNA

What can the cell do if the protein has already been translated?

Answer: The Proteasome! (A Cellular “Garbage Can”!)

Proteins targeted for destruction are firstubiquitinated -Ubiquitin is a small protein that marks a protein for destruction

Ubiquintinated proteins bind to the proteasome, are unfolded, and hydrolyzedinto small peptides which are recycled within the cell

Which Factors Control the Cell Cycle?

Importance of checkpoints and the restriction point

Checkpoint = A “stop or go signal”; progress to the next stageof cell cycle! -Account for progress within each stage (ex. ! complete synthesis of organism’s DNA during S ! phase)

Restriction point = A “enter or exit signal”; commitment to celldivision! -Present between G1 and S stages of interphase ! -Cells that pass the R.P. will divide; cells that do not will! enter G0 (a period of cell cycle arrest or senescence)

The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a “clock”

G1

G1 checkpoint

G1

G0

If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.

Cell Cycle Checkpoints and Restriction Points

Restriction point

3 checkpoints assess the internal state of the cell aswell as the condition ofthe external environment G1/S (restriction point) G2/M M (spindle checkpoint)

• For many cells, the G1/S checkpoint seems to be the most important one

• If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide

• If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase

Importance of the Restriction Point

Which Molecules Regulate Cell Cycle Checkpoints?

Cdk (cyclin-dependent kinase)Major control switches for the cell cycle, causing the cell to move through checkpoints (e.g. G1-->S or G2--> M). -Cdk activation requires binding to a cyclin -Cdks function by phosphorylating molecules in the cell in effect turning them “on” or “off”

Cyclins - Cellular proteins that bind to and activate/inhibit CdksAmount of cyclin protein fluctuates/cycles during cell cycle

Cell Cycle Clock (MPF and G2 --> M checkpoint)

MPF (mitosis promoting factor) -form CyclinB/Cdk1 complexRegulates passage from G2--> M

Begins breakdown of nuclear membrane by phosphorylating (via active cyclin/cdk complex) nuclear lamina proteins

Multiple cyclins and cdks regulate passage through other cell cycle checkpoints

Do Now – Evaluating Cell Cycle CheckpointsUsing what you know about the events of interphase andmitosis, develop a checkpoint strategy for a typical cell.

You may choose the G1/S, G2/M, or mitosis checkpoint

Checkpoint strategy = What would the cell want to do BEFORE entering the next stage of the cell cycle?

Cell Cycle Checkpoints and Restriction Points

G1/Scheckpoint

G2/Mcheckpoint

M(Spindle)

checkpoint

DNA undamaged?Adequate cell size?Sufficient nutrients?

DNA undamaged?DNA replicated? Chromosomes

attached to spindle?

• An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase

• Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide

• For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture

Other Examples of Mitotic/Cell Cycle Regulators

Density-Dependent Inhibition of Cell Growth

Henriettta Lacks and HeLacells -Immortal line of cervical cancer cells

Hayflick number - # of celldivisions is limited in cell culture

Exception to Density-Dependent Inhibition

Chromosome shortening believed to be responsible for cell senescence before cellsreach Hayflick number of celldivisions

One Small Problem with DNA Replication...

Telomerase Animation More on Telomerase

• Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence

Cancer cells do not exhibitanchorage dependenceor density-dependent inhibition.

25 µm

• Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue

• If abnormal cells remain at the original site, the lump is called a benign tumor

• Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors

Cancer Biology

Cancer cell

Bloodvessel

LymphvesselTumor

Glandulartissue Metastatic

tumorA tumor grows from asingle cancer cell.

Cancer cells invadeneighboring tissue.

Cancer cells spreadthrough lymph andblood vessels toother parts of thebody.

A small percentageof cancer cells maysurvive and establisha new tumor in anotherpart of the body.

Growth Factors and Cell Cycle Regulation

PDGFNGFEGFFGFEPO

TGFβ

Gro

wth

fact

ors

Grow

th-inhibiting factors


Exploring the Effects of Growth Factors on Different Types of Cells

Proto-oncogenes (more than 50 currently known)! -Genes that are used to make proteins that promote cell ! division !! -Proto-oncogenes can become oncogenes when ! mutated; oncogenes are always positive regulators! -Proto-oncogenes could encode growth factor receptors! or ANY component of the signaling pathway leading ! from the receptor to the nucleus

Tumor suppressor genes ! -Genes that are used to make proteins that inhibit or ! slow-down cell division/reproduction

Genetics of Cell Cycle Regulation

Example: Ras (small G-protein/GTPase)

Examples: p53, retinoblastoma (Rb)

How a Proto-oncogene Becomes an Oncogene

Genes Involved in Regulation of the Cell Cycleras (Proto-oncogene) - Small G-protein (GTPase)! -Mutated in 20-30% of all human cancers! -Similar to G-protein found at GPCRs but not associated! w/ 7-transmembrane receptors! -Mutated *ras can become an oncogene! ! -Signals to cell nucleus even in the absence of ! ! bound growth factor moleculeRb (Tumor suppressor) [G1 --> S checkpoint]! -Mutated in 40% of all human cancers! -Rb protein usually bound to a transcription factor ! protein (E2F) --> Inactive state! -Cyclin D and cdk4/6 phosphorylate Rb protein during ! late G1 causing Rb to release E2F --> Active state! -E2F acts in the nucleus to turn on genes that promote ! progression through the cell cycle (G1 S)

Retinoblastoma/E2F Signaling Pathway

G1-S Checkpoint: G1 Cyclin-Cdk Cell Cycle Clock (Advanced)

During interphase, Rb protein is bound to the E2F transcriptionfactor

Upon phosphorylation (via an active Cdk), Rb releases E2F

E2F travels to the nucleus where it binds to DNA and initiatesthe transcription of genes involved in advancement throughthe cell cycle

Genes Involved in Regulation of the Cell Cyclep53 (Tumor suppressor) ! -Mutated in approximately 50% of all human cancers! -Monitors integrity of DNA; can “stop” the cell cycle andinitiate DNA repair mechanisms if needed ! -If DNA damage is too severe, p53 can activate a cellsuicide pathway (i.e. apoptosis) leading to cell death! -DNA damage to one copy of p53 increases the risk ofdeveloping tumors because a single detrimental mutation inthe “normal” allele will completely inactivate any p53-mediatedpathway! -DNA damage to both copies of p53 can lead to tumor formation because cells lack the ability to repair DNA damage or commit to apoptosis

A Review of the Genetics of Cell Cycle Regulation

Genes Involved in Regulation of the Cell Cycle

Cell Progressing Through Apoptosis

Apoptosis vs. Necrosis

The Role of p53 in Normal and Cancerous Cells

(If DNA damage cannot be repaired)

DNA damage activatesp53 which leads to the activation of signalingpathways that lead tocell cycle arrest and/orDNA repair

What Are the Potential Causes of Cancer in Organisms?

Cancer cells ignore molecular “switches” at cell cyclecheckpoints! Results in cell reproduction at inappropriate times and! at accelerated rates

Cells become cancerous (are transformed) due to anaccumulation of mutations in cell cycle regulation genes! Mutations in proto-oncogenes and/or tumor suppressor! genes are especially dangerous

In addition, mutations in growth factor receptor genes produceproteins that are always “on” even without bound ligand molecules

chapter 12 mitosis and the cell cycle - parkway schools ... 12 notes.pdf · task – diagramming...

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