2Animation1) What is flight or fight?2) What is glycogen?
312 days until the final How to use this review: 1) Study notes 2) Do questions without notes3) For any questions you are stuck on you can look at your notes or phone a friend4) Use the AP flashcards5) Make a study group6) Ask Morris LOTS of questions7) Know what you know and what you don’t know before the test
4THE CELL CYCLE: Chapter 12 Without counting the G 0 phase, a cell cycle takes hours for most mammalian cells, and only minutes for E. coli cells
5http://highered. mcgraw-hill Take notes on events of each part of the cell cycleInterphase (G1, S, G2) + PMATC
12Mitosis in Action Spindle=_________ Nucleus=_________ Cell Membrane=______Chromosome=______
13Draw the 9 steps of cell cycle G1SG2ProphasePrometaphaseMetaphaseAnaphaseTelophaseCytokinesis
14Take out lab report turn in ONLY if you can answer “Yes” to all questions/statements below 1) My discussion is half a page2) My discussion explain why and not just what happened3) I used 5 or more voc wordsTurn to Lab FRQ packet and start question on page 13 -Animal behavior Look at data table a) summarize pattern (2 points) - Identify three physiological or environmental reason that cause this (3 points)
15The is the 2012 AP Bio Review book. Who wants me to order it for you?
16I can…Write about the role of PROTEINS in the cell cycle
17THE MITOTIC CELL CYCLEThe mitotic phase alternates with interphase in the cell cycleCell Cycle flash animation
18INTERPHASE S G1 (DNA synthesis) Cytokinesis Mitosis G2 MITOTIC LE 12-5INTERPHASES(DNA synthesis)G1CytokinesisMitosisG2MITOTIC(M) PHASE
19What are the key parts of each phase? THE MITOTIC CELL CYCLEThe mitotic phase alternates with interphase in the cell cycleWhat are the key parts of each phase?Mitosis animation
20The 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)
21Review the details of each mitotic phase animal cells (Know the characteristics of the phases)Mitosis flash animation (Purves)
22THE KEY ROLES OF CELL DIVISION Cell division functions in reproduction, growth, and repair
23Cell 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.
24Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus Somatic (nonreproductive) cells have two sets of chromosomesGametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cellsEukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division
25Our DNA is 6 feet long, how does it fit into a nucleus? Note: 10,000 nuclei fit on the tip of your pencil
28Chromosome 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.
30The 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.
34The 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.
35Experimental 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 endsIn a dividing animal cell, non kinetochore microtubules are responsible for elongating the whole cell during anaphase
36Cytokinesis divides the cytoplasm How does it differ in animal and plant cells?
37In 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 myosinThe contraction of the dividing cell’s ring of microfilaments is like the pulling of drawstringsCytokinesis animation
38Cytokinesis 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.
39Mitosis in a plant cellThese light micrographs show mitosis in cells of an onion root.How does this differ from animal cell mitosis?
40Mitosis in eukaryotes may have evolved from binary fission in bacteria Mitosis video (long)
41A 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.
43Regulation 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
44What is Cancer? Cancer means uncontrolled cell growth The body needs to keep cell growth = cell deathCell cycle checkpoints kill mutated or old cells
50How do you get cancer? How can you get cancer? Getting hit in the breast?NOHaving unprotected sex?Smoking?YESBeing in the sun too long?
51Why is cancer so deadly? * 1) Mutated cells beat the cell cycle checkpoints and keep dividing2) They form tumors which then stop your body parts from functioning normally3) Angiogensis – the tumors hijack blood vessels to keep them alive4) Metastisis – the cells from the tumor travel and infect other parts of your body*
53Why is Cancer so Hard to Cure? It is a silent killer, by the time it is found it is already to late2) Chemo/Radiation therapy can kill cancer cells, but is hard on patients3) If one cancer cell survives, or travels, cancer will come back
54Can 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 productsB) choosing foods with less fat and eating more vegetables, fruits, and whole grainsC) exercising regularly and maintaining a lean weightD) avoiding the harmful rays of the sun, using sunblock, and wearing clothing that protects the skin
55Mechanical 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.
56Cell 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 phaseCell Cycle with CheckpointsAnimation
57Many factors are involved in the regulation of the cell cycle
58RB inhibits cell division Active Cdk inhibits RB
59The 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 checkpointsThe 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 constantCyclins vary in the cycle
60Cdks are relatively constant Cyclins vary in the cycle
61The active enzyme and the activating process can be inhibited by two families of cell cycle inhibitory proteins.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.
62Internal and external cues help regulate the cell cycle Internal Signals: Messages from the Kinetochores: the APCA 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.
64Molecular 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 phaseCyclins 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
65Ubiquitin is part of the pathway for the degradation of proteins
66Ubiquitin is part of the pathway for the degradation of proteins
67External 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.
68Density-dependent inhibition of cell division. Most animal cells also exhibit anchorage dependenceCancer cells exhibit neither density-dependent inhibition nor anchorage dependence
69Cancer cells have escaped from cell cycle controls Cancer 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? metastasisBreast cancer animation
70P53 is considered to be a "Guardian of the Genome“ 1. Growth arrest: p21, Gadd45, and s.2. DNA repair: p53R2.3. Apoptosis: Bax, Apaf-1, PUMA and NoxA.
71P53 re-enforces the G2 checkpoint 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.
77Somatic Cells:body cellsEx. ___________Made by mitosisGametes:reproductive cellsEx. ________
78Diploid:Having 2 copies of each chromosome (2n), one from each parentSomatic cells are diploidHuman 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 haploidHuman haploid number is _____What are the cells in your body that are haploid?
79Copy and fill in the chart below. OrganismDiploid # (in somatic cells)Haploid # (in gametes)Cat19Rose12Goat30Rice24Dog39Chimpanzee48
81A pair of chromosomes, 1 from mom and 1 from dad Homologous pair:A pair of chromosomes, 1 from mom and 1 from dadCarry the same genes (ex. eye color gene)But may contain different information (ex. brown eyes and blue eyes)Eye color gene
82Mitosis: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?
89Activity Make 1 set of homologous pairs of chromosomes=2 chromosomes Put letters on the chromosomesDemonstrate crossing overTips: Use whiteboard and move beads
90Game 2: Crossing OverOn page 90 all members need to draw crossing over between homologous chromosomes IN COLORBook pg 276Drawing 1—2 homologous chromosomes with lettersDrawing 2—Crossing over (twisty style)Drawing 3—Final chromosomes
91On the bottom of page 90 write Crossing over occurs between homologous chromosomesThis only occurs in MEIOSISCrossing over occurs during prophase 1 and leads to different sperm and egg
92Dispatch pg 93 Crossing over is when________________ Crossing over occurs during____phase of meiosis
97Draw 4 sperm that are segregated Mendel’s Law 2 pg 92Mendel’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
98Game 4: Segregation or Not? Seat 4—WritesSeat 1--Presents# #2# #4
99Who won? Clean up beads, colored pencils, marker and whiteboard Get ready for exit quiz
100Draw a sperm cell that is segregated Exit QuizDraw a sperm cell that is segregatedDraw 2 alignments for homologous chromosomes in metaphase 1
101Exit Quiz Explain how the cell cycle is regulated How does cancer occur?Give 5 differences between mitosis and meiosis
103Biology is the only subject in which multiplication is the same thing as division… 103
104Why do cells divide? For reproduction For growth For repair & renewal asexual reproductionone-celled organismsFor growthfrom fertilized egg to multi-celled organismFor repair & renewalreplace cells that die from normal wear & tear or from injuryamoebaUnicellular organismsCell division = reproductionReproduces entire organism& increase populationMulticellular organismsCell division provides for growth & development in a multicellular organism that begins as a fertilized eggAlso use cell division to repair & renew cells that die from normal wear & tear or accidents104
105Importance of Cell Division 1. Growth and Development2. Asexual Reproduction Tissue RenewalZygote Embryo Fetus Adult1 Cell cells millions cells 100 trillion cells
106DNA organization in Prokaryotes Nucleoid regionBacterial ChromosomeSingle (1) circular DNASmall(e.g. E. coli is 4.6X106 bp, ~1/100th human chromosome)Plasmids – extra chromosomal DNA
108The Cell Cycle Interphase (90% of cycle) Mitotic phase • G1 phase~ growth• S phase~ synthesis of DNA• G2 phase~ preparation for cell divisionMitotic phase• Mitosis~ nuclear division• Cytokinesis~ cytoplasm division
109Parts of Cell Cycle Interphase M phase G1 S phase G2 Mitosis (Division of nucleus)ProphasePrometaphaseMetaphaseAnaphaseTelophaseCytokinesis (Division of cytoplasm)
110Cell Division: Key Roles Genome: cell’s genetic informationSomatic (body cells) cellsGametes (reproductive cells): sperm and egg cellsChromosomes: condensed DNA moleculesDiploid (2n): 2 sets of chromosomesHaploid (1n): 1 set of chromosomesChromatin: DNA-protein complexChromatids: replicated strands of a chromosomeCentromere: narrowing “waist” of sister chromatidsMitosis: nuclear divisionCytokinesis: cytoplasm divisionMeiosis: gamete cell division
111Chromosome Organization When cells divide, daughter cells must each receive complete copy of DNAEach cell has about 2 meters of DNA in the nucleus; thin threads called chromatinBefore division, condenses to form chromosomesDNA also replicates before cell division to produce paired chromatids111
115Prophase Chromatin condenses visible chromosomes chromatidsCentrioles move to opposite poles of cellanimal cellProtein fibers cross cell to form mitotic spindlemicrotubulesNucleolus disappearsNuclear membrane breaks down
116Prometaphase spindle fibers attach to centromeres creating kinetochoresmicrotubules attach at kinetochoresconnect centromeres to centrioleschromosomes begin moving
117Metaphase Centrosomes at opposite poles Centromeres are aligned Kinetochores of sister chromatids attached to microtubules (spindle)
119Anaphase Paired centromeres separate; sister chromatids liberated Chromosomes move to opposite polesEach pole now has a complete set of chromosomes
120Separation of chromatids In anaphase, proteins holding together sister chromatids are inactivatedseparate to become individual chromosomes1 chromosome2 chromatids2 chromosomessingle-strandeddouble-stranded120
121Chromosome movementKinetochores use motor proteins that “walk” chromosome along attached microtubulemicrotubule shortens by dismantling at kinetochore (chromosome) endMicrotubules are NOT reeled in to centrioles like line on a fishing rod.The motor proteins walk along the microtubule like little hanging robots on a clothes line.In dividing animal cells, non-kinetochore microtubules are responsible for elongating the whole cell during anaphase, readying fro cytokinesis121
122Telophase Cytokinesis begins cell division Daughter nuclei form Nuclear envelopes ariseChromatin becomes less coiledTwo new nuclei complete mitosisCytokinesis beginscell division
127Cytokinesis Animals Cytoplasmic division constriction belt of actin microfilaments around equator of cellcleavage furrow formssplits cell in twolike tightening a draw string
128Cytokinesis in Plants Plants cell plate forms vesicles line up at equatorderived from Golgivesicles fuse to form 2 cell membranesnew cell wall laid down between membranesnew cell wall fuses with existing cell wall128
131Cell Cycle regulation Checkpoints cell cycle controlled by STOP & GO chemical signals at critical pointssignals indicate if key cellular processes have been completed correctly
132Checkpoint control system 3 major checkpoints:G1/Scan DNA synthesis begin?G2/Mhas DNA synthesis been completed correctly?commitment to mitosisspindle checkpointare all chromosomes attached to spindle?can sister chromatids separate correctly?132
133G1/S checkpoint G1/S checkpoint is most critical primary decision point“restriction point”if cell receives “GO” signal, it dividesinternal signals: cell growth (size), cell nutritionexternal signals: “growth factors”if cell does not receive signal, it exits cycle & switches to G0 phasenon-dividing, working state133
134“Go-ahead” signals Protein signals that promote cell growth & division internal signals“promoting factors”external signals“growth factors”Primary mechanism of controlphosphorylationkinase enzymeseither activates or inactivates cell signalsWe still don’t fully understanding the regulation of the cell cycle. We only have “snapshots” of what happens in specific cases.134
135Cell cycle signals Cell cycle controls cyclins Cdks Cdk-cyclin complex inactivated CdkCell cycle controlscyclinsregulatory proteinslevels cycle in the cellCdkscyclin-dependent kinasesphosphorylates cellular proteinsactivates or inactivates proteinsCdk-cyclin complextriggers passage through different stages of cell cycleactivated Cdk135
136External signals Growth factors coordination between cells protein signals released by body cells that stimulate other cells to dividedensity-dependent inhibitioncrowded cells stop dividingeach cell binds a bit of growth factornot enough activator left to trigger division in any one cellanchorage dependenceto divide cells must be attached to a substrate“touch sensor” receptors136
137Growth Factors and Cancer Growth factors can create cancersproto-oncogenesnormally activates cell divisiongrowth factor genesbecome oncogenes (cancer-causing) when mutatedif switched “ON” can cause cancerexample: RAS (activates cyclins)tumor-suppressor genesnormally inhibits cell divisionif switched “OFF” can cause cancerexample: p53137
138Cancer & Cell GrowthCancer is essentially a failure of cell division controlunrestrained, uncontrolled cell growthWhat control is lost?lose checkpoint stopsgene p53 plays a key role in G1/S restriction pointp53 protein halts cell division if it detects damaged DNAoptions:stimulates repair enzymes to fix DNAforces cell into G0 resting stagekeeps cell in G1 arrestcauses apoptosis of damaged cellALL cancers have to shut down p53 activityp53 is the Cell Cycle Enforcerp53 discovered at Stony Brook by Dr. Arnold Levine138
139p53 — master regulator gene NORMAL p53p53 allows cellswith repairedDNA to divide.p53proteinDNA repair enzymep53proteinStep 1Step 2Step 3DNA damage is causedby heat, radiation, orchemicals.Cell division stops, and p53 triggers enzymes to repair damaged region.p53 triggers the destruction of cells damaged beyond repair.ABNORMAL p53abnormalp53 proteincancercellStep 1Step 2DNA damage iscaused by heat,radiation, orchemicals.The p53 protein fails to stopcell division and repair DNA.Cell divides without repair todamaged DNA.Step 3Damaged cells continue to divide.If other damage accumulates, thecell can turn cancerous.139
140Development of CancerCancer develops only after a cell experiences ~6 key mutations (“hits”)unlimited growthturn on growth promoter genesignore checkpointsturn off tumor suppressor genes (p53)escape apoptosisturn off suicide genesimmortality = unlimited divisionsturn on chromosome maintenance genespromotes blood vessel growthturn on blood vessel growth genesovercome anchor & density dependenceturn off touch-sensor geneIt’s like an out-of-control car with many systems failing!140
141What causes these “hits”? Mutations in cells can be triggered byUV radiationchemical exposureradiation exposureheatcigarette smokepollutionagegenetics141
142Tumors Mass of abnormal cells Benign tumor Malignant tumor abnormal cells remain at original site as a lumpp53 has halted cell divisionsmost do not cause serious problems & can be removed by surgeryMalignant tumorcells leave original sitelose attachment to nearby cellscarried by blood & lymph system to other tissuesstart more tumors = metastasisimpair functions of organs throughout body142
145New “miracle drugs”Drugs targeting proteins (enzymes) found only in cancer cellsGleevectreatment for adult leukemia (CML) & stomach cancer (GIST)1st successful drug targeting only cancer cellsProof of Principle: you can treat cancer by targeting cancer-specific proteins.GIST = gastrointestinal stromal tumors, which affect as many as 5,000 people in the United StatesCML = chronic myelogenous leukemia, adult leukemia, which affect as many as 8,000 people in the United StatesFastest FDA approval — 2.5 monthswithout Gleevecwith GleevecNovartes145