Word bank-signaling molecule-cell receptor-signal transduction pathway

-nuclear signaling-cascade-phosphorylation-ATP-protein-response-nucleus-mRNA -second messenger

Animation

• http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html

• 1) What is flight or fight?

• 2) What is glycogen?

12 days until the final

How to use this review:

1) Study notes

2) Do questions without notes

3) For any questions you are stuck on you can look at your notes or phone a friend

4) Use the AP flashcards

5) Make a study group

6) Ask Morris LOTS of questions

7) Know what you know and what you don’t know before the test

THE CELL CYCLE: Chapter 12

Without counting the G 0 phase, a cell cycle takes 12-24 hours for most mammalian cells, and only 20-30 minutes for E. coli cells

• http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__how_the_cell_cycle_works.html

• Take notes on events of each part of the cell cycle

• Interphase (G1, S, G2) + PMATC

Get a whiteboard and beads

Mitosis in the Whitefish blastula

Animal mitosis movie

Mitosis in Action

• Spindle=_________

• Spindle=_________

• Spindle=_________

• Spindle=_________

• Nucleus=_________

• Cell Membrane=______

• Chromosome=______

• Chromosome=______

Draw the 9 steps of cell cycle

• G1• S• G2• Prophase• Prometaphase• Metaphase• Anaphase• Telophase• Cytokinesis

Turn to Lab FRQ packet and start question on page 13

-Animal behaviorLook at data table

a) summarize pattern(2 points)

- Identify three physiological or environmental reason that cause this (3 points)

• Take out lab report turn in ONLY if you can answer “Yes” to all questions/statements below

1) My discussion is half a page 2) My discussion explain why and not just what happened3) I used 5 or more voc words

The is the 2012 AP Bio Review book. Who wants me to order it for you?

I can…

• Write about the role of PROTEINS in the cell cycle

THE MITOTIC CELL CYCLEThe mitotic phase alternates with interphase in the cell cycle

Cell Cycle flash animation

LE 12-5

G1

G2

S(DNA synthesis)

INTERPHASE

Cytokin

esis

MITOTIC(M) PHASE

Mito

sis

THE MITOTIC CELL CYCLE

The mitotic phase alternates with interphase in the cell cycle

Mitosis animation

What are the key parts of each phase?

The stages of mitotic cell division in an animal cell

The light micrographs show dividing lung cells from a newt, which has 22 chromosomes in its somatic cells. The chromosomes appear blue and the microtubules green. (Know the characteristics of the phases)

Review the details of each mitotic phase animal cells(Know the characteristics of the phases)

Mitosis flash animation (Purves)

THE KEY ROLES OF CELL DIVISION   •Cell division functions in reproduction, growth, and repair 

•Cell division distributes identical sets of chromosomes to daughter cells

Eukaryotic chromosomes. A tangle of chromosomes (stained orange) is visible within the nucleus of this kangaroo rat epithelial cell.

• Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus

• Somatic (nonreproductive) cells have two sets of chromosomes

• Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells

• Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division

• Our DNA is 6 feet long, how does it fit into a nucleus?

• Note: 10,000 nuclei fit on the tip of your pencil

http://dnalc.org/view/15491-DNA-packaging-3D-animation-with-narration.html

Chromosome duplication and distribution during mitosis.

Eukaryotic duplicates each of its multiple chromosomes before it divides.

A duplicated chromosome consists of two sister chromatids, which narrow at their centromeres.

What do you know about cytoskeleton?

The mitotic spindle distributes chromosomes to daughter cells

The assembly of spindle microtubules starts in the centrosome, known as a microtubule-organizing center.

During interphase, the single centrosome replicates to form two centrosomes.

During prophase they form spindle fibers and migrate to the poles.

Role of cytoskeleton• http://www.youtube.com/watch?v=5rqbmLiSkpk&feature=related

• http://bio.rutgers.edu/~gb101/lab2_mitosis/section2_frames.html

The mitotic spindle at metaphase

•Each of the two joined chromatids of a chromosome has a kinetochore.

•Anaphase: proteins holding together the sister chromatids of each chromosome are inactivated and they are now full chromosomes.

•Experimental evidence supports the hypothesis that kinetochores use motor proteins that "walk" a chromosome along the attached microtubules toward the nearest pole.

•Meanwhile, the microtubules shorten by depolymerizing at their kinetochore ends

•In a dividing animal cell, non kinetochore microtubules are responsible for elongating the whole cell during anaphase

Cytokinesis divides the cytoplasm

How does it differ in animal and plant cells?

In animal cells, cytokinesis occurs by cleavage

•The cleavage furrow, which begins as a shallow groove in the cell surface.

• On the cytoplasmic side, a contractile ring of actin microfilaments and molecules of the protein myosin

•The contraction of the dividing cell’s ring of microfilaments is like the pulling of drawstrings

Cytokinesis animation

Cytokinesis in plant cells has no cleavage furrow

During telophase, vesicles derived from the Golgi apparatus move along microtubules to the middle of the cell, where they fuse, producing a cell plate.

Mitosis in a plant cell

These light micrographs show mitosis in cells of an onion root.

How does this differ from animal cell mitosis?

Mitosis in eukaryotes may have evolved from binary fission in bacteria

Mitosis video (long)

A hypothesis for the evolution of mitosis

Researchers of eukaryotic cell division have observed in modern organisms what they believe are mechanisms of division intermediate between the binary fission of bacteria and mitosis as it occurs in most eukaryotes.

Cancer

This man has cancer of the mouth.

Regulation of the Cell cycle

The timing and rate of cell division in different parts of a plant or animal are crucial to normal growth, development, and maintenance.

Do all cells have the same cell cycle?

Why is regulation of the cell cycle of interest to research?

Cancer Growth Flash animation

What is Cancer?

• Cancer means uncontrolled cell growth

• The body needs to keep cell growth = cell death

• Cell cycle checkpoints kill mutated or old cells

• http://science.education.nih.gov/supplements/nih1/cancer/activities/activity2_animations.htm

The cell cycle has traffic lights that serve as checkpoints

G1 PhaseS Phase

G2 Phase

Mito

sisCytokinesis

Is the cell ready for mitosis?

Does the body need more cells?

Cancer is caused when the checkpoints are broken and the cell cycle keeps going without stopping

G1 PhaseS Phase

G2 Phase

Mito

sisCytokinesis

What are the types of cancer?*Any part of the body can be cancerous• Skin cancer• Lung cancer• Breast cancer• Testicular cancer• Colon cancer• Liver cancer• Brain cancer

Lung Cancer

Brain Cancer

How do you get cancer?

How can you get cancer?• Getting hit in the breast? NO• Having unprotected sex? NO• Smoking? YES• Being in the sun too long? YES

Why is cancer so deadly?1) Mutated cells beat the cell

cycle checkpoints and keep dividing

2) They form tumors which then stop your body parts from functioning normally

3) Angiogensis – the tumors hijack blood vessels to keep them alive

4) Metastisis – the cells from the tumor travel and infect other parts of your body

*

Here is the development of colon cancer.

Why is Cancer so Hard to Cure?

1) It is a silent killer, by the time it is found it is already to late

2) Chemo/Radiation therapy can kill cancer cells, but is hard on patients

3) If one cancer cell survives, or travels, cancer will come back

Can cancer be prevented?

Cancer is not contagious. There is no guaranteed way to prevent cancer,

people can reduce their risk (chance) of developing cancer by:

A) not using tobacco products B) choosing foods with less fat and eating more

vegetables, fruits, and whole grains C) exercising regularly and maintaining a lean weight D) avoiding the harmful rays of the sun, using

sunblock, and wearing clothing that protects the skin

Mechanical analogy for the cell cycle control system

In this diagram of the cell cycle, the flat "stepping stones" around the perimeter represent sequential events. Like the control device of an automatic washer.

Cell Cycle Checkpoints•A checkpoint is a critical control point where stop and go-ahead signals can regulate the cycle.•The G1 checkpoint (the "restriction point”) is most important. •If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the cycle and divide. •If it does not receive a go-ahead signal at that point, it will exit the cycle, switching into a non-dividing state called the G0 phase.

G0 (G zero)resting phase

Cell Cycle with CheckpointsAnimation

Many factors are involved in the regulation of the cell cycle

RB inhibits cell division

Active Cdk inhibits RB

The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinase

•Fluctuations in the abundance and activity of cell cycle control molecules pace the sequential events of the cell cycle.

•Protein kinases, give the go-ahead signals at the G1 and G2 checkpoints

•The kinases are present at a constant concentration in the growing cell, but much of the time they are in inactive form.

•To be active, such a kinase must be attached to a cyclin, a protein that gets its name from its cyclically fluctuating concentration in the cell.

•These kinases are called cyclin-dependent kinases, or Cdks. The activity of a Cdk rises and falls with changes in the concentration of its cyclin partner.

Cdks are relatively constant

Cyclins vary in the cycle

Cdks are relatively constantCyclins vary in the cycle

The active enzyme and the activating process can be inhibited by two families of cell cycle inhibitory proteins.

1. Members of the INK4 family bind free CDKs thereby preventing association with cyclins.

2. Members of the CIP family bind and inhibit the active CDK-cyclin complex.

http://www.chemsoc.org/exemplarchem/entries/2001/armour/howstrt.htm

Internal and external cues help regulate the cell cycle

Internal Signals: Messages from the Kinetochores: the APC

A gatekeeper at the M phase checkpoint delays anaphase. Regulators from kinetochores insures all the chromosomes are properly attached to the spindle at the metaphase plate and the anaphase-promoting complex (APC) is in an inactive state. When all are attached, the APC then becomes active and indirectly triggers both the breakdown of cyclin and the inactivation of proteins holding the sister chromatids together.

Degradation of key regulator proteins such as the anaphase inhibitors PDS1 and CUT2, and the mitosis initiator cyclin B, drives the cell cycle forward.

Molecular control of the cell cycle at the G2 checkpoint.

The Cdk-cyclin complex called MPF, which acts at the G2 checkpoint to trigger mitosis.

The "maturation-promoting factor" triggers the cell’s passage past the G2 checkpoint into M phase

Cyclins accumulate during G2 associate with Cdk molecules, the resulting MPF complex initiates mitosis.

Later in the M phase, MPF helps switch itself off by initiating a process that leads to the destruction of its cyclin by a protein breakdown mechanism

Ubiquitin is part of the pathway for the degradation of proteins

Ubiquitin is part of the pathway for the degradation of proteins

External Signals: Growth Factors One example of a growth factor is platelet-derived growth factor (PDGF), which is made by blood cells called platelets.

The binding of PDGF molecules to these receptors triggers a signal-transduction pathway that leads to stimulation of cell division.

The proliferation of fibroblasts helps heal the wounds.

Density-dependent inhibition of cell division.

Most animal cells also exhibit anchorage dependence

Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence

Cancer cells have escaped from cell cycle controlsCancer cells do not respond normally to the body’s control mechanisms. They divide excessively and invade other tissues. If unchecked, they can kill the organism.

The growth and metastasis of a malignant breast tumor.

What is a benign tumor? A malignant tumor? metastasis

Breast cancer animation

P53 is considered to be a "Guardian of the Genome“1. Growth arrest: p21, Gadd45, and 14-3-3s. 2. DNA repair: p53R2. 3. Apoptosis: Bax, Apaf-1, PUMA and NoxA.

P53 re-enforces the G2 checkpoint. This serves as a “tumor suppressor” protein.

In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein called p21 that interacts with a cell division-stimulating protein (cdk2). When p21 is complexed with cdk2 the cell cannot pass through to the next stage of cell division. Mutant p53 can no longer bind DNA in an effective way, and as a consequence the p21 protein is not made available to act as the 'stop signal' for cell division. Thus cells divide uncontrollably, and form tumors.

http://highered.mcgraw-hill.com/sites/007337797x/student_view0/chapter9/animation_quiz_-_how_tumor_suppressor_genes_block_cell_division.html

•Explain the following diagram

Mitosis vs. Meiosis

Meiosis

Somatic Cells:•body cells•Ex. ___________•Made by mitosis

Gametes:•reproductive cells•Ex. ________

Diploid:•Having 2 copies of each chromosome (2n), one from each parent•Somatic cells are diploid•Human diploid number is _____What are the cells in your body that are diploid?Are gametes diploid? Why or why not?How many chromosomes does a sperm and egg have?

Haploid:•Having only 1 copy of each chromosome (n)•Gamete cells are haploid•Human haploid number is _____What are the cells in your body that are haploid?

Copy and fill in the chart below.

Organism Diploid # (in somatic cells)

Haploid # (in gametes)

Cat 19

Rose 12

Goat 30

Rice 24

Dog 39

Chimpanzee 48

Eye color gene

Homologous pair:•A pair of chromosomes, 1 from mom and 1 from dad•Carry the same genes (ex. eye color gene)•But may contain different information (ex. brown eyes and blue eyes)

Mitosis:How our bodies make diploid somatic cellsIt happens ________________

Meiosis:The special process of making haploid gametesIt happens in the ______________ & ______________Do you do mitosis?Do you do meiosis?

Meiosis Video 1

Mitosis vs. Meiosis Video

Meiosis

Homologous Chromosomes are Homies

• They are always the same SIZE

• They always have the same type of INFO, but they are not identical

Whiteboard Games

1) All members help to find the answer

2) There will be a seat number who will write and a seat number who will present

Game 1: Whose my Homie?

#1 #2 #3

#4 #5 #6

Seat 2—Writes

Seat 3--Presents

Activity• Make 1 set of homologous pairs of

chromosomes=2 chromosomes

• Put letters on the chromosomes

• Demonstrate crossing over

• Tips: Use whiteboard and move beads

Game 2: Crossing Over

• On page 90 all members need to draw crossing over between homologous chromosomes IN COLOR

• Book pg 276

Drawing 1—2 homologous chromosomes with lettersDrawing 2—Crossing over (twisty style)Drawing 3—Final chromosomes

On the bottom of page 90 write

• Crossing over occurs between homologous chromosomes

• This only occurs in MEIOSIS

• Crossing over occurs during prophase 1 and leads to different sperm and egg

Dispatch pg 93

• Crossing over is when________________

• Crossing over occurs during____phase of meiosis

Mendel’s 2 Laws

Independent Assortment

• http://www.sumanasinc.com/webcontent/animations/content/independentassortment.html

On pg 91 write

• Mendel’s Law of Independent Assortment— homologous chromosomes line up in different combinations during Metaphase I of Meiosis

Draw 2 different alignments

Game 3: 2 alignments for these 2 homies

E e

j J

Mendel’s Law 2 pg 92

• Mendel’s Law of Segregation —allele pairs separate during gamete formation and end up in different gametes (sperm and egg)

Draw 4 sperm that are segregated

Game 4: Segregation or Not?

Seat 4—Writes

Seat 1--Presents

#1 #2

#3 #4

Who won?

• Clean up beads, colored pencils, marker and whiteboard

• Get ready for exit quiz

Exit Quiz

1)Draw a sperm cell that is segregated

2)Draw 2 alignments for homologous chromosomes in metaphase 1

Exit Quiz1) Explain how the cell cycle is regulated

2) How does cancer occur?

3) Give 5 differences between mitosis and meiosis

Chapter 12~ The Cell Cycle

2007-2008

Biology is the only subject in which multiplication is

the same thing as division…

• For reproduction – asexual reproduction

• one-celled organisms

• For growth– from fertilized egg to

multi-celled organism

• For repair & renewal– replace cells that die

from normal wear & tear or from injury

Why do cells divide?

amoeba

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Importance of Cell Division1. Growth and Development

2. Asexual Reproduction 3. Tissue Renewal

Zygote Embryo Fetus Adult1 Cell 100 cells millions cells 100 trillion cells

DNA organization in Prokaryotes

• Nucleoid region

• Bacterial Chromosome – Single (1) circular DNA– Small

• (e.g. E. coli is 4.6X106 bp, ~1/100th human chromosome)

• Plasmids – extra chromosomal DNA

Bacterial Fission

The Cell Cycle• Interphase (90% of cycle) • G1 phase~ growth • S phase~ synthesis of DNA • G2 phase~ preparation for

cell division

• Mitotic phase• • Mitosis~ nuclear division • • Cytokinesis~ cytoplasm

division

Parts of Cell Cycle

• Interphase– G1– S phase– G2

• M phase– Mitosis (Division of nucleus)

• Prophase• Prometaphase• Metaphase• Anaphase• Telophase

– Cytokinesis (Division of cytoplasm)

Cell Division: Key Roles• Genome: cell’s genetic

information• Somatic (body cells) cells• Gametes (reproductive cells):

sperm and egg cells• Chromosomes: condensed DNA

molecules• Diploid (2n): 2 sets of

chromosomes • Haploid (1n): 1 set of

chromosomes• Chromatin: DNA-protein

complex• Chromatids: replicated strands

of a chromosome• Centromere: narrowing “waist”

of sister chromatids• Mitosis: nuclear division• Cytokinesis: cytoplasm division• Meiosis: gamete cell division

111

Chromosome Organization• When cells divide, daughter cells must each

receive complete copy of DNA

• Each cell has about 2 meters of DNA in the nucleus; thin threads called chromatin

• Before division, condenses to form chromosomes

• DNA also replicates before cell division to produce paired chromatids

double-strandedmitotic humanchromosomes

113

Normal Karyotype (Fig 18.1)

Mitosis• Prophase• Prometaphase• Metaphase• Anaphase• Telophase

Prophase

• Chromatin condenses – visible chromosomes

• chromatids

• Centrioles move to opposite poles of cell – animal cell

• Protein fibers cross cell to form mitotic spindle– microtubules

• Nucleolus disappears• Nuclear membrane breaks

down

Prometaphase

– spindle fibers attach to centromeres

• creating kinetochores

– microtubules attach at kinetochores

• connect centromeres to centrioles

– chromosomes begin moving

Metaphase• Centrosomes at

opposite poles• Centromeres are

aligned• Kinetochores of sister

chromatids attached to microtubules (spindle)

Anaphase• Paired centromeres

separate; sister chromatids liberated

• Chromosomes move to opposite poles

• Each pole now has a complete set of chromosomes

Separation of chromatids

• In anaphase, proteins holding together sister chromatids are inactivated– separate to become individual chromosomes

2 chromosomes1 chromosome2 chromatids single-stranded

double-stranded

• Kinetochores use motor proteins that “walk” chromosome along attached microtubule– microtubule shortens

by dismantling at kinetochore (chromosome) end

Chromosome movement

Telophase

• Daughter nuclei form• Nuclear envelopes arise• Chromatin becomes less

coiled• Two new nuclei

complete mitosis

• Cytokinesis begins– cell division

Mitosis in whitefish blastula

Mitosis in plant cell

Cytokinesis

• Cytoplasmic division

• Animals– constriction belt of

actin microfilaments around equator of cell

• cleavage furrow forms

• splits cell in two• like tightening a draw

string

Cytokinesis in Plants• Plants

– cell plate forms• vesicles line up at

equator– derived from Golgi

• vesicles fuse to form 2 cell membranes

– new cell wall laid down between membranes

• new cell wall fuses with existing cell wall

onion root tip

Any Questions??

Cell Cycle regulation

• Checkpoints– cell cycle controlled

by STOP & GO chemical signals at critical points

– signals indicate if key cellular processes have been completed correctly

Checkpoint control system

• 3 major checkpoints:– G1/S

• can DNA synthesis begin?

– G2/M• has DNA synthesis been

completed correctly?• commitment to mitosis

– spindle checkpoint• are all chromosomes attached

to spindle?• can sister chromatids separate

correctly?

G1/S checkpoint

• G1/S checkpoint is most critical

– primary decision point• “restriction point”

– if cell receives “GO” signal, it divides• internal signals: cell growth (size), cell nutrition • external signals: “growth factors”

– if cell does not receive signal, it exits cycle & switches to G0 phase

• non-dividing, working state

“Go-ahead” signals

• Protein signals that promote cell growth & division– internal signals

• “promoting factors”

– external signals• “growth factors”

• Primary mechanism of control– phosphorylation

• kinase enzymes• either activates or inactivates cell signals

Cell cycle signals • Cell cycle controls

– cyclins• regulatory proteins• levels cycle in the cell

– Cdks• cyclin-dependent kinases• phosphorylates cellular proteins

– activates or inactivates proteins

– Cdk-cyclin complex• triggers passage through different stages of

cell cycle

activated Cdk

inactivated Cdk

External signals

• Growth factors– coordination between cells– protein signals released by body

cells that stimulate other cells to divide

• density-dependent inhibition – crowded cells stop dividing

– each cell binds a bit of growth factor

» not enough activator left to trigger division in any one cell

• anchorage dependence – to divide cells must be attached to a

substrate

» “touch sensor” receptors

Growth Factors and Cancer

• Growth factors can create cancers– proto-oncogenes

• normally activates cell division – growth factor genes – become oncogenes (cancer-causing) when mutated

• if switched “ON” can cause cancer• example: RAS (activates cyclins)

– tumor-suppressor genes• normally inhibits cell division• if switched “OFF” can cause cancer• example: p53

Cancer & Cell Growth• Cancer is essentially a failure

of cell division control – unrestrained, uncontrolled cell growth

• What control is lost?– lose checkpoint stops– gene p53 plays a key role in G1/S restriction point

• p53 protein halts cell division if it detects damaged DNA – options:

» stimulates repair enzymes to fix DNA » forces cell into G0 resting stage» keeps cell in G1 arrest » causes apoptosis of damaged cell

• ALL cancers have to shut down p53 activity

p53 discovered at Stony Brook by Dr. Arnold Levine

p53 is theCell CycleEnforcer

DNA damage is causedby heat, radiation, or chemicals.

p53 allows cellswith repairedDNA to divide.

Step 1

DNA damage iscaused by heat,radiation, or chemicals.

Step 1 Step 2

Damaged cells continue to divide.If other damage accumulates, thecell can turn cancerous.

Step 3p53 triggers the destruction of cells damaged beyond repair.

ABNORMAL p53

NORMAL p53

abnormalp53 protein

cancercell

Step 3The p53 protein fails to stopcell division and repair DNA.Cell divides without repair todamaged DNA.

Cell division stops, and p53 triggers enzymes to repair damaged region.

Step 2

DNA repair enzymep53protein

p53protein

p53 — master regulator gene

Development of Cancer

• Cancer develops only after a cell experiences ~6 key mutations (“hits”)– unlimited growth

• turn on growth promoter genes

– ignore checkpoints• turn off tumor suppressor genes (p53)

– escape apoptosis• turn off suicide genes

– immortality = unlimited divisions• turn on chromosome maintenance genes

– promotes blood vessel growth• turn on blood vessel growth genes

– overcome anchor & density dependence• turn off touch-sensor gene

It’s like anout-of-controlcar with manysystems failing!

What causes these “hits”?

• Mutations in cells can be triggered by UV radiation chemical

exposure radiation

exposure heat

cigarette smoke pollution age genetics

Tumors

• Mass of abnormal cells– Benign tumor

• abnormal cells remain at original site as a lump – p53 has halted cell divisions

• most do not cause serious problems &can be removed by surgery

– Malignant tumor• cells leave original site

– lose attachment to nearby cells – carried by blood & lymph system to other tissues– start more tumors = metastasis

• impair functions of organs throughout body

Cancer: breast cancer cell & mammogram

Traditional treatments for cancers

• Treatments target rapidly dividing cells– high-energy radiation

• kills rapidly dividing cells

– chemotherapy• stop DNA replication• stop mitosis & cytokinesis• stop blood vessel growth

New “miracle drugs”

• Drugs targeting proteins (enzymes) found only in cancer cells– Gleevec

• treatment for adult leukemia (CML)& stomach cancer (GIST)

• 1st successful drug targeting only cancer cells

Novartes

withoutGleevec

withGleevec

2008-2009

Any Questions??