1. Today is Monday, December (!) 1 st, 2014 Pre-Class: From where do cells originate? Because they don’t come from this  P.S. Get a paper towel. In This Lesson: Unit 5 Mitosis and the Cell Cycle (Lesson 1 of 3) http://animalsneedkisses.files.wordpress.com/2009/03/teenage_....jpg

2. Today’s Agenda Chromosome basics. The Cell Cycle. Mitosis. – Where division = multiplication. But first… – Class baby pictures. Yes, you. Where is this in my book? – Chapter 12.

3. By the end of this lesson… You should be able to describe a normally- functioning somatic cell cycle and analyze what would happen if it no longer functioned properly. You should be able to identify several chromosomal diseases using karyotypes. You should be able to contrast mitosis and binary fission.

4. A Rather Striking Introduction i am so proud of you – Don Hertzfeldt

5. Class Baby Pictures On the next slide, I have photos of some of you as wee lil’ babies. – Maybe not all, but at least some. Please thank your parents for keeping it a secret. – They did keep it a secret, right? Let’s see…who’s up first…?

6. You. It’s your first diploid cell. The zygote. You all started this way. – You’ve come a long way. http://www.alphascientists.org/images/uploads/images/Zygote_1.jpg

7. Okay then… …let’s get to some Challenge Questions.

8. The Cell Theory Think back to the cell theory… – All living things are made of cells. – Cells are the basic units of structure and function. – All cells come from preexisting cells. That last one is the big one for us right now.

9. You again. You started as a microscopic single cell – a zygote, the cell that resulted from the fusion of gametes – far smaller than the period at the end of this sentence. Aw, you were so cute then…

10. Since then… From that point forward, you’ve been dividing and dividing your cells. – Remember, that’s all you are. Just a bunch of overgrown zygotes. Now you’re a trillion-celled living, breathing, thinking emoting human being with a cell phone addiction.

11. Why Divide? Growth is just one reason. Cell also divide for Reproduction if they’re unicellular. If they’re part of a multicellular organism, they may divide for Repair or renewal, such as when a cut heals or Differentiation, since they need to grow up and get jobs. Not to mention, cells also have to divide because they really can’t get bigger without ruining that whole surface area-to-volume ratio.

12. So what do we need to know? To fully understand the cellular division process, which itself is mostly review of what you’ve already learned, we need to understand the following: – Chromosomes Hey, how do you pronounce that? Dialect Survey! – Karyotyping – The Cell Cycle

13. Chromosomes [Review] Recall that humans have 46 chromosomes arranged in 23 pairs in each of their somatic cells, of which 22 pairs are considered autosomes. – Somatic cells are body cells, as in “not reproductive cells.” – Autosomes are “body chromosomes” – they don’t directly have anything to do with sex characteristics. One pair of chromosomes is the sex chromosomes. – Female = XX; male = XY.

14. Chromosomes [Review] Humans have 46 chromosomes in 23 pairs. – This is a diploid arrangement, also given by the designation 2n – we have 23 chromosomes with 2 copies of each. – Each chromosome in a pair (homologous chromosomes) is similar to the other, one carrying info from mom and one carrying info from dad. It’s like having a pair of shoes. You need both and they are different, but they’re still mostly the same.

15. Chromosomes [Review] Gametes are reproductive cells (such as sperm/ova), and they have a 1n (haploid) arrangement. – Each gamete provides half the BFF necklace/chromosomes needed for a full somatic cell. – When they fuse, the two gametes form a zygote.

16. 1. 2. 3.. 23. Diploid and Haploid MomDad 1. 2. 3.. 23. Diploid Arrangement Homologous Chromosomes Somatic CellsGametes Haploid Arrangement

17. Chromosomes [Review] Dog: 78 Chromosomes (39 pairs) Orangutan: 48 Chromosomes (24 pairs) Mouse: 40 Chromosomes (20 pairs) Strawberry: 56 Chromosomes (7 groups of 8 - octoploid) Adders-tongue fern: 1200 or 1260 Chromosomes Oxytricha trifallax (protozoan): ~16,000 chromosomes

18. Chromosomes [Review] The X chromosome is rather large and has between 800 and 900 genes. – They’re not particularly female-related. Colorblindness and hemophilia are linked to X-chromosome genes, for example. The Y chromosome only has about 40 genes. – They’re called holandric genes, by the way. Therefore, if you inherit a combination of X or Y genes different from XX or XY, interesting changes occur.

19. Chromosomes [Review] XXX – Trisomy X – Female, otherwise healthy. (1 in 1000 females) XXY – Klinefelter Syndrome – Male, reduced sex characteristics, some female characteristics. X0 - Turner Syndrome – Female, appear normal but sterile. XYY – Male, otherwise healthy. (1 in 1000 males).

20. Chromosomes [Review] Chromosomes are often studied in a karyotype. – A karyotype is either: A photo/diagram showing all the chromosomes of an organism/individual, OR The actual chromosomes present in the cell of an organism/individual. Let’s take a look at some…

21. Karyotypes Human Male http://kennethtls.blogspot.com/2010/11/gender-crisis.html

22. Karyotypes Human Female – Turner Syndrome http://kennethtls.blogspot.com/2010/11/gender-crisis.html

23. Karyotypes Human Male – Klinefelter Syndrome http://kennethtls.blogspot.com/2010/11/gender-crisis.html

24. Other Chromosomal Diseases Any case of an abnormal chromosome number is called aneuploidy. For example: – Three copies of chromosome 21? Down Syndrome (Trisomy 21) – Three copies of chromosome 13? Patau Syndrome – Two copies of chromosome X? Female…no, really, this one’s interesting.

25. Females If males can survive with only one X chromosomes, how come females don’t suffer problems with two copies? Turns out, in females, a single X chromosome in each cell is randomly inactivated shortly after conception. The inactivated X chromosome is called a Barr body. – Remember this for a cool fact later. We’ll also talk about how all these aneuploid issues arise.

26. From females to…bacteria? For most of the rest of this PowerPoint we’re going to be discussing eukaryotic somatic cell division (mitosis), but we do need to get something out of the way first: – Binary fission. Binary fission is prokaryotic cell division and it’s pretty simple: – Copy DNA. They only have a single, circular, folded-up DNA molecule. – Divide.

27. Binary Fission

28. Back to Chromosomes [Review] Chromosomes are only visible during mitosis. During other parts of the cell cycle, they’re invisible to a light microscope in a form known as chromatin. – Chromatin is simply DNA wrapped around spherical proteins known as histones. – The histone/DNA complex is known as a nucleosome. https://www.broadinstitute.org/files/news/images/2010/chromatin_states_2a.png

29. And speaking of the cell cycle… The Cell Cycle consists of these stages: G 1 – Gap 1 (growth phase). S – Synthesis (DNA is copied). G 2 – Gap 2 (growth phase). – New organelles are made. M – Mitosis (nucleus divides). Cytokinesis – Cytoplasm divides.

30. The Cell Cycle [Review] There’s also a bonus stage called G 0. – That’s pronounced “G naught.” Cells in G 0 do not divide by mitosis, like brain cells and some muscle cells. – G 0 is thus not part of the cell cycle.

31. The Cell Cycle [Review] G 1, S, and G 2 together make up interphase, the collective name for the “resting phase.” – “Resting phase” is a bad name. The nucleus is present and easy to spot. – DNA is in the form of chromatin.

32. The Cell Cycle [Review] During S phase, all six feet of DNA needs to be copied. – Error rate in copying? 1 in 100 million DNA bases. – With ~30 billion bases in the mammalian genome, that’s around 30 errors each cycle. Not evolution – these are body cells.

33. Terminology [Review] We’re almost there. Before we get into M phase details, there’s one last thing to talk about – chromosome terminology. – It’s gonna get complicated in hurr…

34. Terminology [Review] Chromosome Pre-S PhasePost-S Phase Sister Chromatid S Phase Chromosomes are copied

35. Terminology [Review] Chromatid – Half of a duplicated (X-shaped) chromosome. – Prior to duplication, it was called a chromosome. Sister Chromatids – The two identical chromatid copies that make up an X-shaped chromosome. Centromere – The site at which the two sister chromatids join. – Basically the same as the kinetochore – where spindle fibers (later) will attach.

36. Terminology [Review] Sketch me! http://www.janewhitney.com/img/sister_chromatids.jpg

37. Phew. Time for Mitosis. Key organelles in mitosis: – Nucleus (duh) – Centrioles Aid in cell division, remember? Something new: Centrioles are found in a region of the cell known as the centrosome. There is one centrosome for each of the two pairs of centrioles.

38. Mitosis [Review] What it looks like: http://royaleb.files.wordpress.com/2009/04/mitosis_phases1.jpg

39. Mitosis [Review] What it kinda looks like: http://www.geekosystem.com/wp-content/uploads/2010/07/donut-mitosis.jpeg

40. Mitosis [Review] What it doesn’t look like: http://icanhascheezburger.files.wordpress.com/2008/03/funny-pictures-mitosis-rabbits.jpg

41. Mitosis [Review] Mitosis (M phase) is the division of the nucleus. There are four main phases of mitosis: – Prophase Some people put an additional step here: Prometaphase. – Metaphase – Anaphase – Telophase Got a way to remember these?

42. Prophase [Review] Chromatin condenses into chromosomes. – Chromosomes have been copied by now and look like little X’s. Nuclear membrane/nucleolus breaks down. Mitotic spindle fibers (the “ropes”) forms. – The spindle fibers are made of microtubules (actin/myosin). http://img.sparknotes.com/figures/D/d756b5b73abe2974f3521a828791899f/prophase.gif http://student.ccbcmd.edu/courses/bio141/lecguide/unit6/genetics/DNA/DNArep/images/early_late_prophase1_pc.jpg

43. Prometaphase Prometaphase is an intermediate step between Prophase and Metaphase (obvious). – Starts when the nucleus breaks down and spindle fibers are forming and hooking onto the chromosomes. This centromere/spindle structure is called a kinetochore. – Ends when the chromosomes are being moved into the center of the cell.

44. Metaphase [Review] Chromosomes line up in the middle of the cell at the metaphase plate. – Sometimes called the equator. http://img.sparknotes.com/figures/D/d756b5b73abe2974f3521a828791899f/metaphase.gif http://student.ccbcmd.edu/courses/bio141/lecguide/unit6/genetics/DNA/DNArep/images/metaphase1_ac.jpg

45. Anaphase [Review] Centromeres divide. – Sister chromatids are pulled apart. – Chromatids move toward the poles. http://img.sparknotes.com/figures/D/d756b5b73abe2974f3521a828791899f/anaphase.gif http://student.ccbcmd.edu/courses/bio141/lecguide/unit6/genetics/DNA/DNArep/images/early_anaphase1_pc.jpg

46. Anaphase: Chromosome Movement Some really famous research was devoted to figuring out how chromosomes are brought toward the poles. – Are microtubules (spindle fibers) dismantled near the centrosome or near the kinetochore? It’s the centrosome end that’s shortened.

47. Aside: Spelling Counts Don’t be my former student…

48. Telophase [Review] Nuclear envelope re-forms. For just a little while, there are two nuclei. – These are the daughter nuclei. Chromosomes expand into chromatin. Cytokinesis begins. http://student.ccbcmd.edu/courses/bio141/lecguide/unit6/genetics/DNA/DNArep/images/telophase_ac.jpg http://img.sparknotes.com/figures/D/d756b5b73abe2974f3521a828791899f/telophase.gif

49. Cytokinesis in Animal Cells [Review] The cell divides into two daughter cells. A belt of actin microfilaments pinches the membrane together between nuclei – forms a cleavage furrow. Cell walls are a little different (next slide). http://img.sparknotes.com/figures/D/d756b5b73abe2974f3521a828791899f/cytokinesis.gif http://www.bio.miami.edu/~cmallery/150/mitosis/sf8x9a.jpg

50. Cytokinesis in Plant Cells [Review] Cell plate forms from vesicles, which themselves form a pair of cell membranes (sent from Golgi). – Cell wall is inside the vesicle membrane. Cell wall forms on top of the cell plate, dividing the cell into two daughter cells. http://student.ccbcmd.edu/courses/bio141/lecguide/unit6/genetics/DNA/DNArep/images/telophase2_pc.jpg http://wpcontent.answers.com/wikipedia/commons/thumb/5/5b/Phragmoplast.png/300px-Phragmoplast.png

51. Cytokinesis in a Plant Cell

52. Mitosis in a Plant Cell

53. Mitosis in Onion Roots

54. Mitosis in Animal Cells

55. Mitosis in Whitefish

56. Mitosis Summary This really cool company called Hybrid Medical Animations put together an awesome CGI look at mitosis in a cell. http://www.hybridmedicalanimation.com/wo rk/animation/the-stages-of-mitosis/ http://www.hybridmedicalanimation.com/wo rk/animation/the-stages-of-mitosis/

57. Mitosis Scope Activity Okay, here’s a change-of-pace. At each of your lab tables is a microscope along with a slide showing mitosis in onion root tips. Take a look around the slide and, with your group, see if you can spot cells in different stages of mitosis. – As I walk by, point some out to me. – Make sure you all rotate in to view the scope. – Hint: where on the root would mitosis be happening most? – Lastly, don’t goof off. Just because there aren’t any questions doesn’t mean you can’t learn from this. Triple negative?

58. Summary of Mitosis 46 Start with one diploid cell that has 46 chromosomes. Mitosis End with two cells called? They each have how many chromosomes? Two diploid daughter cells each with 46 chromosomes

59. Mitosis What it actually really looks like (see the spindles?): http://www.geekosystem.com/wp-content/uploads/2010/07/donut-mitosis.jpeg

60. Mitosis Fun Facts 300,000,000 cells die and are replaced every minute – roughly equal to the population of the United States. 50,000,000 cells are born in the time it takes me to read this. Nerve cells do not divide but are replaced from glial cells through neurogenesis.

61. Aside: How Old Are You? While it’s true that cells divide relatively quickly, they also don’t last forever. Right now, the oldest cells in your body are 7- 9 years old. – That’ll stay the same throughout your life – always 7-9 years old, max, for your cells… …which means that nothing living about you is actually as old as…you. – Whoooooooa.

62. Mitosis Rap Yep, not kidding…we’re going to listen to a mitosis rap. – I didn’t do it…could you have guessed?

63. Mitosis Rap Lyrics “I” is for Interphase is step 1 the step before mitosis has begun. “P” is for Prophase is step 2 the chromosome double dog that’s what they do. “M” is for Metaphase is step 3 the chromosomes line up as you can see. “A” is for Anaphase is step 4 as chromosomes move away from the core. “T” is for Telophase is step 5, right two daughter cells are made in both of our life…a’ight. Mitosis tells all my cells to divide. Each cells put chromosomes to opposite sides. It makes daughter cells that are two of a kind, two of a kind.

64. Other Mitosis Stuff Mitosis App – https://itunes.apple.com/us/app/mitosis/id34818 4626?mt=8 https://itunes.apple.com/us/app/mitosis/id34818 4626?mt=8 Mitosis – Phase Contrast Microscope

65. Cell Division Practice Time for a Quia quiz: Labeling Mitosis. – This one’s important! Leave your computer on but closed when you’re done.

66. Cell Cycle Game Grab yo’ laptops and find The Cell Cycle Game: http://nobelprize.org/educational/medicine/2001/in dex.html – Also linked from my Biology Links page. Complete the Quia activity called Cell Cycle Game. Keep an eye on the dial in the upper left corner and the “energy” in the upper right!

67. Back to the Cell Cycle You’ve now reviewed all of the cell cycle, from interphase through mitosis and cytokinesis. – That’s the “what,” as in, “what is the cell cycle?” We now need to talk about the regulation of the cell cycle. – This is the “how,” as in, “how does the cell manage this whole process and keep it from getting out of control?

68. Cell Cycle Regulation Imagine, for a moment, what it would be like if all cells in a bear had the same cycle? – One moment it’d just be sitting there, the next moment it would be TWICE AS HUGE. Normal growth and maintenance of a multicellular creature thus requires careful coordination of cell division.

69. Cell Division Frequency First of all, how long does it take the average cell to divide? – Embryonic cells = <20 minutes – Skin cells = 12-24 hours – Liver cells = 1-2 years (tend not to divide) Liver cells stay in G 0 but can return to the cell cycle if signaled. – Nerve and muscle cells = never (after maturity)

70. Cell Cycle Control As you saw in the game, throughout the cell cycle are several checkpoints. – During G 1 to ensure that S phase can begin. This is the most important signal. If the cell doesn’t get a “go,” it enters G 0. – After G 2 to check that S phase went smoothly and division can occur safely. – During M phase (spindle checkpoint) to be certain that spindles have attached to chromosomes correctly.

71. Checkpoints http://skreened.com/scienceforscientists/dna-checks-itself-before-it-wrecks-itself

72. Cell Cycle Signals Okay, I’ve been mentioning “signals” a lot without being specific. Here’s the cast of characters. Internal Signals – Cyclins – regulatory proteins whose levels cycle (get it?). – Cdks – cyclin-dependent kinases that phosphorylate (activate) cellular proteins. – MPF – a mitosis promoting factor. External Signals – Density-dependent inhibition – cells are inhibited from growing if there are a ton of cells around them. – Anchorage dependence – cells need to grow on a substrate.

73. Cyclins and Cdk A cyclin is a protein molecule. – That’s it. It can’t do anything on its own. There are cyclins for just about every stage in the cell cycle. For example: – G 1 -phase cyclin – G 1 /S-phase cyclin – S-phase cyclin – M-phase cyclin Key: Their concentration varies throughout the cell cycle.

74. Cyclins and Cdk A Cdk is a cyclin-dependent kinase. – It’s a kinase, so it phosphorylates stuff to activate it. – As you might guess, it needs cyclin to work. Key: Cdk concentration is stable throughout the cell cycle. Cdks bind to cyclins as they are produced. Key: Once Cdk activity passes a certain threshold, the entire cell is driven into the next phase of the cell cycle.

75. Cyclins and CDK Activity http://www.nature.com/scitable/topicpage/cdk-14046166

76. Cyclins and Cdk Hey…wait a second. Does something about cyclins and Cdk sound vaguely familiar? Like…maybe…this?

77. From Cyclin to Cdk to… Since Cdks, which are themselves just enzymes, play a VERY important role once complexed to a cyclin, the Cdk/cyclin complex is known as an MPF (for mitosis promoting factor).

78. MPFs and APC In addition to the general MPF (mitosis promoting factor), there is also an APC – anaphase promoting complex. – Anaphase promoting complex surges in concentration during metaphase…promoting anaphase as the next step. By now you’re probably getting the idea that there are lots of signals in play. In general: – The main control mechanism is phosphorylation as carried out by kinases. – Internal signals are promoting factors. – External signals are growth factors.

79. External Signals (Growth Factors) External signals, like we’ve learned before, are released by cells and have effects on others. What kind of effects? Density-dependent inhibition is when crowded cells don’t divide anymore. Why? – Growth factors released by cells are bound by so many other cells that no one can get enough growth factor to divide.

80. External Signals (Growth Factors) It’s like this: – Suppose we are feeding two people with a pizza. Fine. Each person will probably get enough to be full. AKA each cell gets enough growth factor to divide. – Now suppose we’re feeding two thousand people with a pizza. People simply aren’t going to get enough to be full. AKA each cell doesn’t get enough growth factor to divide.

81. Anchorage Dependence Cells, spoiled lil’ buggers that they are, have touch receptors that need to be on a proper substrate to grow. – Substrate as in “growing surface,” not enzyme-y stuff. This is called anchorage dependence. Cue the video: NOVA – Artificial Organ Growth

82. Case in Point: Growth Factor Let’s take an in-depth look at a growth factor and related processes. This is a fantastic review of a lot of stuff we’ve learned so far. – Anything important that we’ve reviewed will be underlined. – Anything new and important will be bold and underlined. The growth factor? – Platelet-Derived Growth Factor (PDGF)

83. Case in Point: Growth Factor The story starts with erythropoietin (EPO), which is a glycoprotein hormone made by the kidney. When renal (kidney) oxygen levels drop too low, kidneys release EPO which stimulates bone marrow to make more red blood cells. – Thus the blood can now carry more oxygen, thus enabling greater ATP production through aerobic respiration. This is a negative feedback loop.

84. Case in Point: Growth Factor In that way, EPO is a GF of red blood cells. Ever hear about EPO in the news? Coughlancearmstrongcough… Coughblooddopingcough… http://upload.wikimedia.org/wikipedia/commons/thumb/4/47/Lance_Armstrong_%28Tour_Down_Under_2009%29.jpg/430px-Lance_ Armstrong_%28Tour_Down_Under_2009%29.jpg and Lance_Armstrong_MidiLibre_2002.jpg/800px-Lance_Armstrong_MidiLibre_2002.jpg

85. Case in Point: Growth Factor EPO has been used as a performance-enhancing drug (PED) (in this case known as “blood doping”) because it increases the oxygen-carrying capacity of the blood by making it extra rich with blood cells. The downside? – All those extra blood cells makes your blood considerably thicker/more viscous. – Dehydration also makes your blood thicker/more viscous. – Thick/viscous blood = increased risk of stroke/heart attack/death. Just say no to EPO.

86. Case in Point: Growth Factor But there’s another growth factor involved here. – “Another GF? Scandalous!” Forget EPO for a second. Suppose you get a paper cut. http://farm3.static.flickr.com/2062/1892872952_b4e38a6edc.jpg

87. Case in Point: Growth Factor Platelets in the blood near your cut bind to the neighboring skin cells. They release PDGF (platelet-derived growth factor, remember?). PDGF stimulates neighboring skin cells to divide, healing your wound. – Also, platelets stimulate more platelets to arrive and release more PDGF, making this an example of a positive feedback loop. http://th05.deviantart.net/fs71/PRE/i/2012/102/d/3/paper_cut__by_xcrazyonyoux-d4vw2dj.jpg

88. So the logical question… We have all these checkpoints. What happens if something goes wrong. In a word? – Cancer. Many cancers are caused by cells that escape from the normal cell cycle. – The brakes on cell division have been removed. Normal cells divide up to 60 times or so (more on this in a little bit). – Cancer cells? A lot more. TED: George Zaidan – How Cancer Cells Behave Differently from Healthy Ones

89. Case in Point: HeLa Cells Many cancer cells used in research are called HeLa cells. – Named for Henrietta Lacks, a poor African- American woman from the South. In 1951, Lacks sought treatment for cervical cancer. Her doctor(s) took a tissue sample from a tumor and cultured it. – “Cultured” meaning “grew in a lab.” Lacks died later in the year, with her family not knowing that her cells had been cultured. – Today, her cells are still living and dividing endlessly and are used in research all over the world. – Read that book! 

90. Cancer Terminology Tumor – A mass of cancer cells. Remember, cancer cells divide A LOT. – Benign tumors are sitting in their original spot. – Metastatic or malignant tumors are spreading throughout the body. Carcinogen – Something that causes cancer. Like smoking, chewing tobacco, or other things CB students do in bathrooms.

91. Cancerous Growth Factors Proto-oncogenes are genes that cause cancer if switched “on” and mutated. – Ras is a group of genes like this and are involved in 30% of human cancers. Tumor-suppressor genes cause cancer if switched “off.” – p53 is a tumor-suppressor gene and is involved in 50% of human cancers. So it follows that mutagens are things that cause mutations and may also be carcinogens.

92. Cancerous Growth Factors Another factor in play is the degradation of telomeres. Telomeres are “caps” on the ends of the chromosomes that are made of junk DNA. – With each cell division, however, telomeres get smaller. http://www.psychologytoday.com/files/u693/telomere.jpg

93. Aside: The Hayflick Limit In the 1960s, Leonard Hayflick discovered that there was a limit to how many times cells could divide before their telomeres were eroded completely away. – That number is somewhere between 52 and 60 times, and it’s now called the Hayflick Limit. After that point, the cells may either be told to die (apoptosis – programmed cell death) or simply won’t divide anymore. http://www.nature.com/polopoly_fs/7.11184.1372152253!/image/Hayflick28.jpg_gen/derivatives/landscape_630/Hayflick28.jpg

94. Cancer Growth Factors Mutagens/Carcinogens – UV radiation Tanning beds! – Chemicals – Radiation – Heat – Pollution – Cigarette smoke Other Factors – Age – Genetics

95. How does cancer work? Cancerous genes or cells are often found to be activating lots of cyclins, thus pushing the cell through the cell cycle too rapidly. Tumor suppressor genes prevent errant DNA from being copied in mitosis. – p53, for example, stops cell division if bad DNA is found, but if p53 isn’t working…you get the idea. Subsequent growth and spread of tumors can begin to block blood vessels, clog body systems, prevent other cells from functioning…the list goes on…

96. Case in Point: p53 DNA damage is caused by heat, radiation, or chemicals. p53 allows cells with repaired DNA to divide. Step 1 DNA damage is caused by heat, radiation, or chemicals. Step 1 Step 2 Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous. Step 3 p53 triggers the destruction of cells damaged beyond repair. ABNORMAL p53 abnormal p53 protein cancer cell Step 3 The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA. Cell division stops, and p53 triggers enzymes to repair damaged region. Step 2 DNA repair enzyme p53 protein p53 protein NORMAL p53

97. Cancer Mutations There are six key mutations that must happen for cancer to occur: 1.Unlimited growth – Growth promoter genes turned on. 2.Ignore checkpoints – Tumor suppressor genes turned off. 3.Escape apoptosis – Suicide genes turned off. 4.Immortality – Chromosome maintenance genes turned on. 5.Blood vessel growth – Blood vessel growth genes turned on. 6.Anchorage/density-independence – Touch sensor genes turned off.

98. Cancer Treatments High-Energy Radiation – Kill rapidly-dividing cells. Chemotherapy – Stop DNA replication, mitosis/cytokinesis, and blood vessel growth. Gleevec – A relatively new anti-cancer drug that targets enzymes found only in cancer cells. Guess what? It also doesn’t cause autism.

99. Exit Ticket Before this lesson ends, you must get a small disposable piece of paper and on it write the following: – Your name. – How prokaryotes divide. – The official definition of mitosis. – What two molecules combine to regulate the cell cycle. You can’t leave until you do this. I’m serial. Put ‘em in the turn-in box on your way out.