1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Chapter 19 Eukaryotic Genomes: Organization, Regulation, and Evolution

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview: How Eukaryotic Genomes Work and Evolve In euk’s, the DNA-protein complex, called chromatin – Is ordered into higher structural levels than the DNA-protein complex in prokaryotes Figure 19.1

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Both prok’s & euk’s alter their patterns of gene expression in response to changes in environmental cond’s

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 19.1: Chromatin structure is based on successive levels of DNA packing Euk DNA – precisely combined w/ a lg amt of protein Euk chromo’s – have an enormous amount of DNA relative to their condensed length

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Nucleosomes, or “Beads on a String” Proteins- histones (+) – 1 st level of DNA (-) packing in chromatin – Bind tightly to DNA assoc of DNA & histones – Seems to remain intact throughout the cell cycle

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In electron micrographs – Unfolded chromatin looks like beads on a string Nucleosome- “beads” r basic unit of DNA packing Figure 19.2 a 2 nm 10 nm DNA double helix Histone tails His- tones Linker DNA (“string”) Nucleosome (“bad”) Histone H1 (a) Nucleosomes (10-nm fiber)

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Nucleosome 30 nm (b) 30-nm fiber Higher Levels of DNA Packing next level of packing – Forms the 30-nm chromatin fiber Figure 19.2 b

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The 30-nm fiber, in turn – Forms looped domains, making up a 300-nm fiber Figure 19.2 c Protein scaffold 300 nm (c) Looped domains (300-nm fiber) Loops Scaffold

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In a mitotic chromosome – The looped domains themselves coil and fold forming the characteristic metaphase chromosome Figure 19.2 d 700 nm 1,400 nm (d) Metaphase chromosome

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings interphase cells – Euchromatin– chromatin in the highly extended form (available 4 txn) – Heterochromatin– condensed/tightly packed state in interphase (usually no txn)

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 19.2: Gene expression can be regulated at any stage, key step is txn All organisms – Must regulate which genes are expressed at any given time During development of a multicellular organism – cell differentiation- cells undergo a process of specialization in form & function

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Differential Gene Expression Each cell of a multicellular euk – Expresses only a fraction of its genes In each type of differentiated cell – A unique subset of genes is expressed

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Many key stages of gene expression – Can be regulated in euk cells Figure 19.3 Signal NUCLEUS Chromatin Chromatin modification: DNA unpacking involving histone acetylation and DNA demethlation Gene DNA Gene available for transcription RNA Exon Transcription Primary transcript RNA processing Transport to cytoplasm Intron Cap mRNA in nucleus Tail CYTOPLASM mRNA in cytoplasm Degradation of mRNA Translation Polypetide Cleavage Chemical modification Transport to cellular destination Active protein Degradation of protein Degraded protein

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Regulation of Chromatin Structure Genes w/in highly packed heterochromatin – Are usually not expressed

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Histone Modification Chem modification of histone tails – Can affect the configuration of chromatin & thus gene expression Figure 19.4a (a) Histone tails protrude outward from a nucleosome Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation DNA double helix Amino acids available for chemical modification Histone tails

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Histone acetylation – Seems to loosen chromatin structure & so enhances txn Figure 19.4 b (b) Acetylation of histone tails promotes loose chromatin structure that permits transcription Unacetylated histones Acetylated histones

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings DNA Methylation Adding methyl groups to certain bases in DNA – is assoc w/ reduced txn in some spp

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Epigenetic Inheritance Epigenetic inheritance – inheritance of traits transmitted by mechanisms not directly involving the nt seq

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Regulation of Transcription Initiation Regulation of Txn Initiation: Chromatin-modifying enzymes control gene expression – By making a region of DNA either more or less able to bind the txn machinery

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Organization of a Typical Eukaryotic Gene Assoc’d w/ most euk genes are multiple control elements – Segments of noncoding DNA that help regulate txn by binding certain proteins Figure 19.5 Enhancer (distal control elements) Proximal control elements DNA Upstream Promoter Exon IntronExon Intron Poly-A signal sequence Exon Termination region Transcription Downstream Poly-A signal ExonIntron Exon IntronExon Primary RNA transcript (pre-mRNA) 5 Intron RNA RNA processing: Cap and tail added; introns excised and exons spliced together Coding segment P P P G mRNA 5 Cap 5 UTR (untranslated region) Start codon Stop codon 3 UTR (untranslated region) Poly-A tail Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Cleared 3 end of primary transport

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Roles of Transcription Factors To initiate txn – Euk RNA pol needs help of proteins called txn factors

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Enhancers and Specific Transcription Factors Proximal control elements – close to promoter Distal control elements, groups of which are called enhancers – far away from a gene or in an intron

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Distal control element Activators Enhancer Promoter Gene TATA box General transcription factors DNA-bending protein Group of Mediator proteins RNA Polymerase II RNA Polymerase II RNA synthesis Transcription Initiation complex Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation A DNA-bending protein brings the bound activators closer to the promoter. Other transcription factors, mediator proteins, and RNA polymerase are nearby. 2 Activator proteins bind to distal control elements grouped as an enhancer in the DNA. This enhancer has three binding sites. 1 The activators bind to certain general transcription factors and mediator proteins, helping them form an active transcription initiation complex on the promoter. 3 activator – protein that binds to an enhancer & stimulates txn of a gene Figure 19.6

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Some txn factors act as repressors – To inhibit expression of a particular gene Some activators & repressors – Act indirectly by influencing chromatin structure

25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Combinatorial Control of Gene Activation A particular combination of control elements can activate txn only when the appropriate activator proteins are present Figure 19.7a, b Enhancer Promoter Control elements Albumin gene Crystallin gene Liver cell nucleus Lens cell nucleus Available activators Available activators Albumin gene expressed Albumin gene not expressed Crystallin gene not expressed Crystallin gene expressed (a) (b) Liver cell Lens cell

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Liver & lens cells have genes for albumin & crystallin Which txn factors (activators & repressors) are made in a specific type of cell determine which genes are expressed They share a control element but each enhancer has a diff comb of elements

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Coordinately Controlled Genes Unlike the genes of a prok operon – Coordinately controlled euk genes each have a promoter & control elements The same regulatory seq’s – Are common to all the genes of a group, enabling recognition by the same specific txn factors

28. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mechanisms of Post-Transcriptional Regulation An ↑ing # of examples – Are being found of regulatory mechanisms that operate at various stages after txn

29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings RNA Processing alternative RNA splicing – Diff mRNA molecules are made from the same primary transcript, depending on which RNA segments are treated as exons & which as introns Figure 19.8 Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Exons DNA Primary RNA transcript mRNA RNA splicing or

30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings mRNA Degradation life span of mRNA molecules in the cytoplasm – impt factor in determining the protein synthesis in a cell – Is determined in part by seq’s in the leader & trailer regions

31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings RNA interference by ss microRNAs (miRNAs) – Can lead to degradation of an mRNA or block its tsln Figure 19.9 5 Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Degradation of mRNA OR Blockage of translation Target mRNA miRNA Protein complex Dicer Hydrogen bond The micro- RNA (miRNA) precursor folds back on itself, held together by hydrogen bonds. 1 2 An enzyme called Dicer moves along the double- stranded RNA, cutting it into shorter segments. 2 One strand of each short double- stranded RNA is degraded; the other strand (miRNA) then associates with a complex of proteins. 3 The bound miRNA can base-pair with any target mRNA that contains the complementary sequence. 4 The miRNA-protein complex prevents gene expression either by degrading the target mRNA or by blocking its translation. 5

32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Initiation of Translation initiation of tsln of selected mRNAs – Can be blocked by regulatory proteins that bind to specific seq’s or structures of the mRNA Alternatively, tsln of all the mRNAs in a cell – May be regulated simultaneously – RNAi is thought to have originated as a defense against RNA viruses b/c it can destroy RNA’s

33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Protein Processing and Degradation After tsln – Various types of protein processing, including cleavage & adding chem grps, are subject to control

34. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Proteasomes – Are giant protein complexes that bind protein molecules & degrade them Figure 19.10 Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Ubiquitin Protein to be degraded Ubiquinated protein Proteasome and ubiquitin to be recycled Protein fragments (peptides) Protein entering a proteasome Multiple ubiquitin mol- ecules are attached to a protein by enzymes in the cytosol. 1 The ubiquitin-tagged protein is recognized by a proteasome, which unfolds the protein and sequesters it within a central cavity. 2 Enzymatic components of the proteasome cut the protein into small peptides, which can be further degraded by other enzymes in the cytosol. 3

35. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 19.3: Cancer results from genetic changes that affect cell cycle control The gene regulation systems that go wrong during cancer – Turn out to be the very same systems that play important roles in embryonic development

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Types of Genes Associated with Cancer Types of Genes Assoc w/ Cancer genes that normally regulate cell growth & division during the cell cycle – genes for growth factors, their receptors, & the intracellular molecules of signaling pathways

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Oncogenes and Proto-Oncogenes Oncogenes – Are cancer-causing genes Proto-oncogenes – normal cellular genes that code for proteins that stimulate normal cell growth & division

38. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings DNA change that makes a proto-oncogene excessively active – Converts it to an oncogene, which may promote excessive cell division and cancer Figure 19.11 Proto-oncogene DNA Translocation or transposition: gene moved to new locus, under new controls Gene amplification: multiple copies of the gene Point mutation within a control element Point mutation within the gene Oncogene Normal growth-stimulating protein in excess Hyperactive or degradation- resistant protein Normal growth-stimulating protein in excess Normal growth-stimulating protein in excess New promoter

39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Proto-oncogenes convert to oncogenes via: 1-Mvmt of DNA w/in genome (transposable elements) 2-Amplification of a proto-oncogene 3-Point mutation in control element or the proto-onco gene itself

40. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tumor-Suppressor Genes Tumor-suppressor genes – Encode proteins that inhibit abnormal cell division

41. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Interference with Normal Cell-Signaling Pathways Many proto-oncogenes & tumor suppressor genes – Encode components of growth-stimulating and growth-inhibiting pathways, respectively

42. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.12a (a) Cell cycle–stimulating pathway. This pathway is triggered by a growth factor that binds to its receptor in the plasma membrane. The signal is relayed to a G protein called Ras. Like all G proteins, Ras is active when GTP is bound to it. Ras passes the signal to a series of protein kinases. The last kinase activates a transcription activator that turns on one or more genes for proteins that stimulate the cell cycle. If a mutation makes Ras or any other pathway component abnormally active, excessive cell division and cancer may result. 1 2 4 3 5 GTP Ras GTP Hyperactive Ras protein (product of oncogene) issues signals on its own NUCLEUS Gene expression Protein that stimulates the cell cycle P P P P MUTATION P DNA P Ras protein, encoded by the ras gene – a G protein that relays a signal from a growth factor receptor on the pm to a cascade of protein kinases 2 Receptor Transcription factor (activator) 5 G protein 3 Protein kinases (phosphorylation cascade) 4 1 Growth factor

43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings p53 gene encodes a tumor-suppressor protein – a specific txn factor that promotes the synthesis of cell cycle–inhibiting proteins Figure 19.12b UV light DNA Defective or missing transcription factor, such as p53, cannot activate transcription MUTATION Protein that inhibits the cell cycle pathway, DNA damage is an intracellular signal that is passed via protein kinases and leads to activation of p53. Activated p53 promotes transcription of the gene for a protein that inhibits the cell cycle. The resulting suppression of cell division ensures that the damaged DNA is not replicated. Mutations causing deficiencies in any pathway component can contribute to the development of cancer. (b) Cell cycle–inhibiting pathway. In this 1 3 2 Protein kinases 2 3 Active form of p53 DNA damage in genome 1

44. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mutations that knock out the p53 gene – lead to excessive cell growth & cancer Figure 19.12c EFFECTS OF MUTATIONS Protein overexpressed Cell cycle overstimulated Increased cell division Cell cycle not inhibited Protein absent Effects of mutations. Increased cell division, possibly leading to cancer, can result if the cell cycle is overstimulated, as in (a), or not inhibited when it normally would be, as in (b). (c)

45. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Multistep Model of Cancer Development Normal cells are converted to cancer cells – By the accumulation of multiple mutations affecting proto-oncogenes & tumor-suppressor genes

46. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings A multistep model for the development of colorectal cancer Figure 19.13 Colon Colon wall Normal colon epithelial cells Small benign growth (polyp) Larger benign growth (adenoma) Malignant tumor (carcinoma) 2 Activation of ras oncogene 3 Loss of tumor- suppressor gene DCC 4 Loss of tumor-suppressor gene p53 5 Additional mutations 1 Loss of tumor- suppressor gene APC (or other)

47. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Certain viruses – Promote cancer by integration of viral DNA into a cell’s genome

48. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inherited Predisposition to Cancer Indiv’s who inherit a mutant oncogene or tumor-suppressor allele – Have an ↑d risk of getting certain types of cancer

49. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 19.4: Euk genomes can have many noncoding DNA seq’s in addition to genes bulk of most euk genomes – Consists of noncoding DNA sequences, often described in the past as “junk DNA” However, much evidence is accumulating – That noncoding DNA plays important roles in the cell

50. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Relationship B/w Genomic Composition and Organismal Complexity Compared w/ prok genomes, euk’s – Generally are larger – Have longer genes – Contain a much > amt of noncoding DNA both associated w/ genes & b/w genes

51. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Now that the complete sequence of the human genome is available – We know what makes up most of the 98.5% that does not code for proteins, rRNAs, or tRNAs Figure 19.14 Exons (regions of genes coding for protein, rRNA, tRNA) (1.5%) Repetitive DNA that includes transposable elements and related sequences (44%) Introns and regulatory sequences (24%) Unique noncoding DNA (15%) Repetitive DNA unrelated to transposable elements (about 15%) Alu elements (10%) Simple sequence DNA (3%) Large-segment duplications (5-6%)

52. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Transposable Elements and Related Sequences The 1 st evidence for wandering DNA segments – Came from geneticist Barbara McClintock’s breeding experiments w/ Indian corn Figure 19.15

53. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Transposon New copy of transposon Transposon is copied DNA of genome Insertion Mobile transposon (a) Transposon movement (“copy-and-paste” mechanism) Retrotransposon New copy of retrotransposon DNA of genome RNA Reverse transcriptase (b) Retrotransposon movement Insertion Movement of Transposons and Retrotransposons Euk transposable elements, 2 types; – 1. Transposons, move w/in a genome by means of a DNA intermediate – 2. Retrotransposons, move by means of an RNA intermediate (retroviruses may have evolved from these) Figure 19.16a, b

54. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sequences Related to Transposable Elements Multiple copies of transposable elements & seq’s related to them – scattered through the euk genome – Amphibians & plants have more (spontaneous new spp via transposable elements??) humans & other primates – A lg portion of transposable element–related DNA consists of a family of similar seq’s called Alu elements (which don’t code for proteins but RNA w/no known function)

55. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other Repetitive DNA, Including Simple Sequence DNA Simple seq DNA (microsatellites) --many copies of tandemly repeated short seq’s – common in centromeres & telomeres, where it probably plays structural roles in the chromosome

56. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genes and Multigene Families Most euk genes – Are present in 1 copy per haploid set of chromo’s The rest of the genome – Occurs in multigene families, collections of identical or very similar genes

57. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings DNA RNA transcripts Non-transcribed spacer Transcription unit DNA 18S5.8S28S rRNA 5.8S 28S 18S Some multigene families – Consist of identical DNA seq’s, usually clustered tandemly, such as those that code for RNA products Figure 19.17a Part of the ribosomal RNA gene family

58. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The classic examples of multigene families of nonidentical genes – Are 2 related families of genes that encode globins Figure 19.17b The human  -globin and  -globin gene families  -Globin Heme Hemoglobin  -Globin  -Globin gene family  -Globin gene family Chromosome 16Chromosome 11 Embryo Fetus and adult Embryo FetusAdult  GG AA        22  11 22 11 

59. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 19.5: Duplications, rearrangements, & mutations of DNA contribute to genome evolution basis of change at the genomic level is mutation – Which underlies much of genome evolution

60. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Duplication of Chromosome Sets Duplication of Chromosome Sets: Accidents in cell division – lead to xtra copies of all or part of a genome, which may then diverge if 1 set accumulates seq changes

61. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Duplication and Divergence of DNA Segments Duplication & Divergence of DNA : Unequal crossing over during prophase I of meiosis – Can result in 1 chromosome w/ a deletion & another w/ a duplication of a particular gene Figure 19.18 Nonsister chromatids Transposable element Gene Incorrect pairing of two homologues during meiosis Crossover and

62. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evolution of Genes with Related Functions: The Human Globin Genes The genes encoding the various globin proteins – Evolved from 1 common ancestral globin gene, which duplicated & diverged Figure 19.19 Ancestral globin gene          22  11 22 11   GG AA    -Globin gene family on chromosome 16  -Globin gene family on chromosome 11   Evolutionary time Duplication of ancestral gene Mutation in both copies Transposition to different chromosomes Further duplications and mutations

63. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Subsequent duplications of these genes & random mutations – Gave rise to the present globin genes, all of which code for oxygen-binding proteins

64. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The similarity in the aa seq’s of the various globin proteins – Supports this model of gene duplication and mutation Table 19.1

65. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evolution of Genes with Novel Functions copies of some duplicated genes – Have diverged so much during evolutionary time that the functions of their encoded proteins are now substantially diff

66. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Rearrangements of Parts of Genes: Exon Duplication and Exon Shuffling Rearrangements of Parts of Genes: Exon Duplication & Shuffling An exon w/in a gene – Could be duplicated on 1 chromo & deleted from the homologous chromo

67. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings exon shuffling – Errors in meiotic recomb can lead to mixing & matching of diff exons either w/in a gene or b/w 2 nonallelic genes Figure 19.20 EGF Epidermal growth factor gene with multiple EGF exons (green) F FF F Fibronectin gene with multiple “finger” exons (orange) Exon shuffling Exon duplication Exon shuffling K FEGFK K Plasminogen gene with a “kfingle” exon (blue) Portions of ancestral genesTPA gene as it exists today

68. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How Transposable Elements Contribute to Genome Evolution Mvmt of transposable elements or recomb b/w copies of the same element – can generate new seq comb’s that are beneficial to the organism Some mechanisms – Can alter the functions of genes or their patterns of expression & regulation

69. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ch 19 overview Chromatin structure-levels of DNA packing Regulating gene experession- @ chromatin structure (methylation ↓’d txn, acetylation-loosens chromatin ↑’d txn) @ txn initiation-control elements (distal/enhancer & proximal) depends on which type of activators are in that cell Post-txn-alternative RNA splicing, microRNA’s

70. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ch 19 overview regulation of gene expression cont’ Tsln initiation-initiation factors Past tsln-protein processing, cleaving the pp, adding chem groups to pp (ubiquitin/proteasomes)

71. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ch 19 overview Cancer results from genetic changes Products of proto-onco genes & tumor suppressor genes control cell division DNA changes to proto-onco gene change it to an onco-gene (causing ↑’d cell division) Mutation in tumor suppressor gene Mutation in Ras gene causes ↑’d cell division P53 mutation fails to act as a tumor suppressor

72. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ch 19 Relationship b/w genome composition & organism complexity -transposable elements Simple seq DNA-short noncoding regions repeated many times

73. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ch 19 overview Multiple mutations in proto-onco genes Viruses can also cause genetic changes that lead to cancer Some types are inherited