1. LECTURE PRESENTATIONS For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson © 2011 Pearson Education, Inc. Lectures by Erin Barley Kathleen Fitzpatrick Control of DNA Chapter 12 & 18

2. The Cell Cycle cell cycle = ordered series of events that lead to cell division and the production of 2 daughter cells each with the same # and type of chromosomes as the parent 2 key events in the cell cycle –1. chromosome replication –2. chromosome segregation consists of two phases –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 sub- phases G 1 phase -“first gap” S phase “synthesis” G 2 phase - “second gap”

3. Nobel Prize? You bet! Leland Hartwell Tim Hunt Paul Nurse 2001 https://plus.google.com/+Nobel Prize/posts

4. Eukaryotic Cell Cycle Control 2 major events take place during the cell cycle –duplication of the chromosomes (S phase) –duplicated chromosomes are distributed to the daughter cells (M phase)

5. -parent cell = cell about to undergo division -daughter cell = cell that results from either mitosis or meiosis -somatic cell = any cell within the body other than an egg or sperm -somatic cell has two complete sets of chromosomes -one set is called the haploid number of chromosomes (n) -therefore the cell is said to be diploid (2n) e.g. humans n = 23 (2n = 46) -germ cell or gamete = sex cell -gamete has only one set of chromosomes and is haploid Some terms to know

6. two kinds of eukaryotic cell division –Mitosis –Meiosis eukaryotic cell division consists of –Mitosis - the division of the genetic material in the nucleus –Cytokinesis - the division of the cytoplasm mitosis described by the German anatomist Walther Flemming in 1882 –thought the cell was simply growing larger between each period of cell division –now known that the growing cells were in the G1 phase –never observed the M phase Eukaryotic Cell Division

7. Some terms to know -parent cell = cell about to undergo division -daughter cell = cell that results from either mitosis or meiosis -somatic cell = any cell within the body other than an egg or sperm -somatic cell has two complete sets of chromosomes -one set is called the haploid number of chromosomes (n) -therefore the cell is said to be diploid (2n) e.g. humans n = 23 (2n = 46) -germ cell or gamete = sex cell -gamete has only one set of chromosomes and is haploid

8. Most cell division results in genetically identical daughter cells most cell division results in daughter cells with identical genetic information (i.e. amount and type of DNA) the genetic information has to be duplicated and distributed amongst the two daughter cells once the DNA is duplicated and distributed then the cell can divide SO: cell division is not just the pinching of the parent cell into two daughter cells

9. Cellular Organization of the Genetic Material all the DNA in a cell constitutes the cell’s genome REMINDER: when not dividing – much of the eukaryotic DNA is in its loosest formation = chromatin –a complex of DNA and protein that condenses during cell division –allows access to the machinery for DNA replication and transcription 20  m

10. 0.5  m Centromere Sister chromatids in preparation for cell division - DNA is replicated and condenses into chromosomes chromosome = organized structure of DNA and protein –chroma = color –soma = body the building material of a chromosome is chromatin each duplicated chromosome is made of two sister chromatids = joined copies of the original chromosome –these chromatids will separate during cell division and be partitioned into each daughter cell chromatids are joined by a structure called a centromere every eukaryotic species has a characteristic number of chromosomes in each cell nucleus e.g. humans – n=23 e.g. drosophila – n=2 e.g. dog – n=39

11. 0.5  m Centromere Sister chromatids Centromere location along the chromosome – two sister chromatids are joined condensed region within the chromosome responsible for the accurate segregation of sister chromatids during mitosis & meiosis shared by sister chromatids during mitosis site of the centromere where spindle microtubules attach – area of DNA and protein = kinetochore

12. Kinetochore a structure of DNA (CEN DNA) and proteins located in the centromere for the attachment of the chromosome to the spindle during mitosis and meiosis one MT attaches to one kinetochore on one chromatid a 2 nd MT attaches to the kinetochore on the other chromatid attachment of these MTs results in movement toward the poles a “tug of war” results – chromosomes move back and forth and eventually settle in the metaphase plate Inner Plate Outer Plate Microtubules Kinetochore Chromatid Microtubules

13. Chromosome and Chromosome: Confusion!!! prior to cell division – the duplicated chromatin condenses into its most dense form = chromosome –two sister chromatids joined by a centromere –typically called a duplicated chromosome during cell division - the two sister chromatids separate once separated - the chromatids are still called chromosomes

14. Control of DNA Structure: Condensation of Chromatin shortest human chromosome is 44 million nucleotides long this means packing 14000 um (14mm) of linear DNA into a nucleus around 2um that is a 7000:1 packing ratio!!! packing is achieved by the chromatin chromosome scaffold http://www.ndsu.edu/pubweb/~mcclean/plsc431/eukarychrom/eukaryo3.htm

15. Control of DNA Structure: Condensation of Chromatin nucleosome = DNA helix wrapped around a histone protein core –responsible for organizing the DNA as chromatin –10 nm and 30 nm fibers other proteins in nuclear lamina are involved organizing chromatin as the chromosome these nuclear lamina proteins = non-histone proteins NHPs form a chromosome scaffold the heterochromatin is “looped” onto this scaffold –megabase, long-loops of 30nm heterochromatin associated with this scaffold  300nm fiber chromosome scaffold

16. Control of DNA Structure: Condensation of Chromatin specific sequences in the chromosome called scaffold- associated regions or SARs interact with the scaffold to create the 300 nm fiber last level of “packing” is a 700 nm fiber –not much known about this –the chromosome seen in metaphase chromosome scaffold

17. Mitosis is conventionally divided into five phases –Prophase –Prometaphase –Metaphase –Anaphase –Telophase Cytokinesis overlaps the latter stages of mitosis

18. G 2 of InterphaseProphasePrometaphase Centrosomes (with centriole pairs) Chromatin (duplicated) Nucleolus Nuclear envelope Plasma membrane Early mitotic spindle Aster Centromere Chromosome, consisting of two sister chromatids Fragments of nuclear envelope Nonkinetochore microtubules Kinetochore Kinetochore microtubule Metaphase Metaphase plate AnaphaseTelophase and Cytokinesis Spindle Centrosome at one spindle pole Daughter chromosomes Cleavage furrow Nucleolus forming Nuclear envelope forming 10  m

19. Mitosis http://www.loci.wisc.edu/outreach/bioclips/CDBio.html Spindle – structure that includes the two centrioles, two asters and the spindle microtubules than span the cell Aster – a radial array of short MTs extending from the centrioles 1.Prophase: prior to prophase, the replicated DNA is starting to condense into sister chromatids joined at the centromere  (duplicated) chromosome 1. the centrioles (replicated at G2) move apart from each other 2. the nucleoli disappear

20. Spindle Formation 3. the kinetochore forms in the centromere 4. the spindle forms between the centrioles (made of microtubules) -the centrioles are not essential for spindle formation; plant cells do not have centrioles -spindle MT assembly results from the polymerization of tubulin subunits -other MTs of the cytoskeleton disassemble to provide more tubulin to the spindle Spindle – structure that includes the two centrioles, two asters and the spindle microtubules that span the cell Aster – a radial array of short MTs extending from the centrioles

21. 3.Metaphase: centrioles are at opposite ends of the cell and the spindle is complete 1. the chromosomes move and line up along a central zone= metaphase plate -the tug of war at pro-metaphase eventually positions the chromosomes midway alone the length of the cell 2. non-kinetochore MTs interact with the opposite pole & the aster MTs make contact with the plasma membrane – the spindle is now complete 10  m Metaphase 3

22. 4. Anaphase: shortest of the mitotic phases 1. the chromatid pairs separate into daughter chromosomes 2. one chromatid/chromosome moves toward one centriole of the cell, the other the opposite -pulled apart by the action of the spindle – the kinetochore MTs begin to shorten -PLUS non-kinetochore MTs grow – this elongates the cell ** At the end of this phase – each end of the cell has equivalent numbers of chromosomes – same number as the parent cell **the sister chromatids separate because of enzymatic activity -an enzyme called separase cleaves a protein known as cohesin (protein in the centromere that holds the sister chromatids together) -separates the sister chromatids

23. 4. Telophase: reverse of Prophase 1. nuclear envelope reforms – two daughter nuclei result -part of the new nuclear membrane is recycled from the old fragments, other parts are made new by the cell 2. the nucleoli reappear 3. the spindle disappears as the MTs depolymerize 4. daughter chromosomes uncoil ** Cytokinesis starts during late anaphase and is well underway during telophase

24. Cytokinesis: division of cytoplasm -separates the parent into two daughter cells -differs in animal cells and plant cells Animal cell Cytokinesis: results from cleavage - pinches into two daughters -actin filaments assemble to form a contractile ring along the equator of the cell -actin interacts with myosin proteins – causes the ring to contract -actin-myosin interaction first forms a “cleavage furrow” - slight indentation around the circumference of the cell -continued interaction divides the cell by a “purse string” mechanism (a) Cleavage of an animal cell (SEM) Cleavage furrow Contractile ring of microfilaments Daughter cells 100  m

25. (b) Cell plate formation in a plant cell (TEM) Vesicles forming cell plate Wall of parent cell Cell plate New cell wall Daughter cells 1  m Plant cell Cytokinesis: No cleavage furrow possible -vesicles bud from the Golgi apparatus and migrate to the middle of the cell -vesicles coalesce to produce a cell plate -other vesicles fuse to the plate bringing in new building materials -cell plate grows and eventually splits the cell into two daughter cells 10  m Telophase 5 Cell plate

28. Binary Fission in Bacteria bacteria and archaea reproduce by binary fission –the chromosome replicates and the two daughter chromosomes actively move apart –the plasma membrane pinches inward, dividing the cell into two –BUT there is no ordered segregation of the duplicated chromosome –duplicate it and divide it into two cells 1 Origin of replication E. coli cell Two copies of origin Cell wall Plasma membrane Bacterial chromosome Origin Chromosome replication begins. Replication continues. Replication finishes. Two daughter cells result. 2 3 4

29. The Evolution of Mitosis mitosis probably evolved from binary fission certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis (a) Bacteria (b) Dinoflagellates (d) Most eukaryotes Intact nuclear envelope Chromosomes Microtubules Intact nuclear envelope Kinetochore microtubule Fragments of nuclear envelope Bacterial chromosome (c) Diatoms and some yeasts

30. Phases of the Cell Cycle consists of two phases –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 sub-phases –G 1 phase -“first gap” –S phase “synthesis” –G 2 phase - “second gap”

31. Phases of the Cell Cycle –G 1 phase - time in phase depends on species normal cell functions & growth in size mRNA and protein synthesis in preparation for S phase critical phase in which cell commits to division or leaves the cell cycle to enter into a dormancy phase (G0) –S phase - 6 to 8 hours synthesis of histone proteins & DNA replication –G 2 phase – 2 to 5 hours rapid cell growth protein synthesis in preparation for M phase duplication of the centrioles/centrosomes http://www.wisc- online.com/objects/in dex.asp?objID=AP136 04

32. Cell Cycle Checkpoints interphase not only allows the cell to perform its normal functions but also allows the cell to check whether it is ready to enter mitosis cell cycle is controlled by a control system that coordinates and triggers key events in the cell cycle progression through the cell cycle requires a combination of internal and external signals these signals control whether the cell is ready to continue on into the S and M phases

33. Eukaryotic Cell Cycle Control EXPERIMENT: fusion of two cells at different points in the cell cycle –Results in “re-setting” of one cell to coordinate with the other CONCLUSION: cell division is driven by specific chemical signals present in the cytoplasm Experiment 1 Experiment 2 S SS G1G1 G1G1 M MM EXPERIMENT RESULTS When a cell in the S phase was fused with a cell in G 1, the G 1 nucleus immediately entered the S phase—DNA was synthesized. When a cell in the M phase was fused with a cell in G 1, the G 1 nucleus immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.

34. Cell Cycle Checkpoints so the control system of the cell cycle monitors these signals and determines whether to proceed through the cell cycle there are specific points along the cell cycle where “decisions” are made by this control system = CHECKPOINTS cancer cells manage to escape the usual controls on the cell cycle

35. major checkpoints – G1, G2 and M –G1 checkpoint – G1/S progression through a point called the restriction point or START point of the cell cycle –G2 checkpoint – G2/M progression which will lead to the start of mitosis and chromosome alignment –M checkpoint – Metaphase to Anaphase transition where chromatid separation occurs Cell Cycle Checkpoints G 1 checkpoint G1G1 G2G2 G 2 checkpoint M checkpoint M S Control system

36. for many cells, the G1/S checkpoint seems to be the most important –if a cell receives a go-ahead signal at this G1/S checkpoint  will usually complete the S, G 2, and M phases and divide –many texts call this checkpoint the Start (yeasts) or Restriction point (mammalian cells) if the cell does not receive the go-ahead signal - will exit the cycle, switching into a non-dividing state called the G 0 phase most cells in the body are in the G0 phase and remain there some cells have the ability to leave G0 and re-enter the cell cycle Cell Cycle Checkpoints G 1 checkpoint G1G1 G1G1 G0G0 (a) Cell receives a go-ahead signal. (b) Cell does not receive a go-ahead signal.

37. IN ANIMAL CELLS A “GO-AHEAD” SIGNAL MUST BE PRODUCED TO OVERRIDE A BUILT IN “STOP” SIGNAL

38. the proteins of this system evolved over a billion years ago so well conserved in eukaryotes – take from human control cells and put into yeast cells – they work!! much of the early research done –done in yeast –search for mutations in genes that encode critical parts of the cell cycle control system = cell-division-cycle genes or cdc genes –many mutations in this family of genes causes the cell cycle to arrest at specific points – such as checkpoints additional work done in frog eggs and in mammalian cell cultures –e.g. immortalized mammalian cell lines Cell Cycle Control System

39. The Cell Cycle Control System: Cyclins and Cyclin- Dependent Kinases two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks) –cyclins named for the cyclical changes in their concentration through the cell cycle –cdks named because their phosphorylation activities requiring their binding to their “partner” cyclin –cdks cannot work as kinases unless they are bound to their partner cyclin the cdk-cyclin complex is called a heterodimer

40. Cyclins and Cyclin-Dependent Kinases –cyclin/CDKs regulate the activities of multiple proteins by the cdk phosphorylating them –Cyclin/CDK partners are involved in: 1. entry to the cell cycle (i.e. G1 phase) 2. DNA replication (i.e. S phase) 3. segregation of chromosomes during mitosis (i.e. M phase)

41. The Cell Cycle Control System: Cyclins and Cyclin- Dependent Kinases cdk activity fluctuates during the cell cycle –cdk proteins are expressed first –activity is controlled by an array of proteins - including the cyclins –cyclical changes in cdk activities leads to cyclical changes in the phosphorylation of their target proteins –cdks phosphorylate key proteins responsible for passing through each checkpoint

42. The Cell Cycle Control System: Cyclins and Cyclin- Dependent Kinases eukaryotic cells have four classes of cyclins –each act at a specific stage of the cell cycle –eukaryotic cells require three of these classes for their cell cycle 1. G1/S cyclins 2. S-cyclins 3. M-cyclins

43. The Cell Cycle Control System: Cyclins and Cyclin- Dependent Kinases 1. G1/S cyclins – active in late G1; trigger the progression through the G1 restriction point (START) 2. S-cyclins – activate cdks that help stimulation chromosome duplication + they help initiate mitosis –e.g. the cdk phosphorylates proteins that activate DNA helicases G1/S cyclins: levels peak during G1 S cyclins: levels slowly climb and stay high until Mitosis

44. The Cell Cycle Control System: Cyclins and Cyclin- Dependent Kinases 3. M-cyclins – activate the cdks that stimulate progression through the G2 checkpoint and into Mitosis –Cdk phosphorylate numerous proteins involved in chromosome segregation and other aspects of mitosis M cyclins: levels climb during G2 and drop just after metaphase checkpoint

45. Cyclins and Cyclin-Dependent Kinases – no you don’t have to know these for your exam!!! FUNCTION G1/entry into cell cycle Entry into cell cycle & S phase Mitosis modified from Cell Biology Alberts et al.

46. (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle MPF activity Cyclin concentration Time M M M S S G1G1 G2G2 G1G1 G2G2 G1G1 work in frog eggs identified a cdk-cyclin complex that triggered the cell’s passage past the G 2 checkpoint into the M phase called MPF (maturation-promoting factor) also called Mitosis-promoting factor –cyclin B and CDK1 now known to act in all eukaryotic mitotic cells Cyclins and CDKs in action

47. cyclin B synthesis begins in late S phase and increases through G2 and into M cyclin B combines with CDK1 in G2 to produce MPF when enough MPF is made – the cell passes the G2 checkpoint and enters Mitosis MPF promotes Mitosis via CDK1 phosphorylating its target proteins –e.g. phosphorylated target proteins results in nuclear envelope fragmentation Cyclins and CDKs in action

48. (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle (b) Molecular mechanisms that help regulate the cell cycle MPF activity Cyclin concentration Time M M M S S G1G1 G2G2 G1G1 G2G2 G1G1 Cdk Degraded cyclin Cyclin is degraded MPF G 2 checkpoint Cdk Cyclin M S G1G1 G2G2 want to control the CDK? control the expression of the cyclin!!! the most important regulatory control of a cyclin is its degradation e.g. during anaphase cyclin B becomes degraded and CDK1 activity starts to fall –the cdk1 part of the MPF actually degrades its partner cyclin –the cdk1 is “recycled” for future cycles M phase stops and G1 begins Regulation of CDK activity

49. activation of specific cyclin-cdk complexes also drive progression through the G1 and G2 checkpoints progression through the M checkpoint requires the degradation of proteins e.g. degradation of cyclin B one key regulator of cyclin degradation is the anaphase-promoting complex or APC mitotic cdk/cyclin complexes induce chromosome condensing, breakdown of the nuclear envelope, assembly of the spindle and the alignment of chromosomes –this gets you up to Anaphase once this happens – the sister chromatids must separate at Anaphase the APC controls this Degradation of cyclins and cell cycle control

50. mitotic cdk/cyclins activate the APC (via phosphorylation) the APC directs the degradation of proteins that act as anaphase inhibitors in the cell allows the onset of anaphase Degradation of cyclins and cell cycle control cyclin/cdk APC activates cessation of mitosis anaphase degradation of inhibitors

51. BUT as mitosis proceeds – the APC also directs the degradation of the cdk/cyclin complex increasing APC levels act through negative feedback the drop in mitotic cdk/cyclin complexes now allows for the condensing of chromosomes etc….. and the cessation of mitosis Degradation of cyclins and cell cycle control promotes degradation cyclin/cdk APC activates cessation of mitosis anaphase degradation of inhibitors

52. Stop and Go Signs: Internal and External Signals at the Checkpoints there is a link between what is happening inside and outside the cell with the activity of cdk/cyclins in other words – internal and external signals exert control over cdk/cyclins and the cell cycle internal signal – e.g. kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase –Because all chromosomes must be attached to the spindle in order to eventually activate the enzyme called separase

53. some external signals are growth factors –proteins released by certain cells that stimulate other cells to divide = mitogen A sample of human connective tissue is cut up into small pieces. Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. Cells are transferred to culture vessels. Scalpels Petri dish PDGF is added to half the vessels. Without PDGF With PDGF 10  m 1 2 3 4 platelet-derived growth factor (PDGF) stimulates the division of platelet in the body stimulates the division of human fibroblast cells in culture –PDGF binds to PDGF receptors on the fibroblast –initiate the progression through the G1 phase into M Growth factors as External Signals at the Checkpoints

54. Stop and Go Signs: Internal and External Signals at the Checkpoints some external signals are growth factors –proteins released by certain cells that stimulate other cells to divide = mitogen another external signal - density-dependent inhibition –crowded cells stop dividing another signal - anchorage dependence –cells must be attached to a substrate in order to divide

55. Loss of Cell Cycle Controls in Cancer Cells Glandular tissue Tumor Lymph vessel Blood vessel Cancer cell Metastatic tumor A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Cancer cells spread through lymph and blood vessels to other parts of the body. Cancer cells may survive and establish a new tumor in another part of the body. 4321 cancer cells exhibit neither density-dependent inhibition nor anchorage dependence Cancer = known medically as a malignant neoplasm cells with upregulated cell growth because they do not have a normally controlled cell cycle uncontrolled division gives rise to cells that can invade surrounding tissues and travel through the lymphatic and circulatory systems to invade other tissues at a distance = malignant cancer if abnormal cells remain only at the original site - the lump is called a benign tumor

56. Mutagen – agent that causes a mutation in the DNA Carcinogen – mutagens that causes cancer

57. Mutagens mutagen = agent that causes a mutation in the DNA mutations can arise in a number of ways –1. errors in replication –2. errors in genetic recombination (during meiosis) mutagens can be both physical and chemical agents –physical – X-rays, UV light other forms of high energy radiation –chemical – nucleotide analogs (mimic a NT but incorrectly pair), intercalating agents, others alter chemical properties of the base (alters their pairing capacity) types of mutations: –small scale – point mutations –large scale – effect large areas of chromosome sequence

58. Mutations small-scale mutations = point mutations: A. nucleotide/base pair substitutions – replacement of one NT and its partner for another pair if there is no change to the eventual codon/amino acid = silent mutation if it changes the amino acid to a stop codon = nonsense mutation if it changes the amino acid = missense mutation –still may be no change to the overall structure and function of the protein

59. Mutations Wild type DNA template strand mRNA 5 5 Protein Amino end 3 3 5 MetLysPheGly Stop Carboxyl end TTTTT TTTTTAAAAA AAAACC C C A AAAAA GGGG G CC GGGUUUUUG 3

60. Mutations B. insertions C. deletions insertions and deletions can lead to a frame-shift alters how the codons are read downstream from the mutation

61. Mutations & Frameshifts Wild type DNA template strand mRNA 5 5 Protein Amino end 3 3 5 MetLysPheGly Stop Carboxyl end TTTTT TTTTTAAAAA AAAACC C C A AAAAA GGGG G CC GGGUUUUUG 3

62. Large scale deletions effect larges areas of DNA in chromosomes Numerous kinds: 1. translocations 2. duplications 3. inversions 4. deletions

63. two broad category of genes affected with these mutations: tumor-suppressor genes and proto-oncogenes Genes of Cancer

64. Oncogene – gene with the potential to cause cancer Many are derived from proto-oncogenes = normal cellular genes responsible for normal cell growth and division –mutation in a proto-oncogene transforms them into an oncogene conversion of a proto-oncogene to an oncogene can lead to abnormal stimulation of the cell cycle Genes of Cancer: Oncogenes

65. Oncogene oncogenes result in abnormal cell cycle control checkpoints e.g. Cyclin D –in normal cells – cyclin D is a link between G1 progression and growth factor production –mutation  overproduction of cyclin D in cancer cells drives the cell into and through this phase acts to shorten the G1 phase –even takes cells out of the G0 phase sooner then they should be

66. oncogenes can result from: –translocation of DNA within the genome: if it ends up near an active promoter, transcription may increase –amplification of a proto-oncogene: increases the number of copies of the gene via gene duplication –point mutations in the proto-oncogene or its control elements: cause an increase in gene expression Genes of Cancer: Oncogenes Proto-oncogene DNA Translocation or transposition: gene moved to new locus, under new controls Gene amplification: multiple copies of the gene New promoter Normal growth- stimulating protein in excess Point mutation: within a control element within the gene Oncogene Normal growth- stimulating protein in excess Hyperactive or degradation- resistant protein

67. Oncogene Translocation e.g. Philadelphia chromosome Translocation between chromosomes 9 and 22 fusion chromosome 22 and chromosome 9 results Area of fusion produces a fusion between two genes – BCR and ABL1 A fusion protein results = BCR-ABL This fusion protein has high kinase activity – phosphorylates target proteins involved in cell cycle control Loss of cell cycle control associated with Chronic Myelogenous Leukemia

68. Genes of Cancer: Tumor-Suppressor Genes tumor-suppressor genes help prevent uncontrolled cell growth –mutations that decrease protein products of tumor-suppressor genes may contribute to cancer onset tumor-suppressor proteins –repair damaged DNA –control cell adhesion –inhibit the cell cycle using cell-signaling pathways most studied tumor suppressor gene/protein = p53 –functions as an inhibitor to the cell cycle when DNA damage is sensed by repair mechanisms –ensures that the DNA is repaired before proceeding to mitosis

69. Cancer Therapies treatments of tumors –1. chemotherapy – targets rapidly proliferating cells –2. radiation –3. immune therapies – antibody therapy e.g. Herceptin, Avastin –4. hormone therapies - Tamoxifen –5. STIs – signal transduction inhibitors other promising approaches such a nanotechnology –coupling of drugs to nanoparticles capable of entering a cancer cell quite easily –internalization releases drug once inside cell –increase targeting of nanoparticle by coupling particle/drug to an antibody specific to a cancer cell

70. Mutations in Cancer genetic mutations can result in the transformation of the genes of cell growth and differentiation –required for the development of cancer numerous kinds of genetic mutations possible – more than one is usually required –small scale point mutations, deletions and insertions  large scale deletion or gain of chromosomal sections, translocation of chromosome sections