2. Chapter 11 Gene Expression http://www.youtube.com/watch?v=oBwtxdI1zvk&feature=related

3. What is gene expression? DNA RNA Proteins Turning “on” and “off” genes Don’t need specific proteins all the time Make them when you need them

4. Gene Expression in Prokaryotes E. coli (bacteria that live in intestines of mammals) Discovered how genes control the metabolism of the sugar lactose Lactose: disaccharide made of glucose and galactose Milk sugar

5. When there is/is not lactose LACTOSE PRESENT: It induces E. coli to produce three enzymes which will metabolize lactose LACTOSE ABSENT: three enzymes will not be made. Lactose will not be broken down.

6. Operon: series of genes that code for specific products and the regulatory elements that control these genes Lac operon: segment of DNA that codes for the enzymes that regulate lactose metabolism

7. DNA of E.coli Regulator gene: codes for repressor gene Promoter: DNA segment that is recognized by the enzyme RNA pol Operator: DNA segment that serves as a “switch” controlling the access of RNA pol to the promoter Structural genes: code for 3 enzymes that break down lactose

8. Operon “turned off” Repressor protein attaches to the operator physically blocking RNA pol from attaching RNA pol

9. Operon “turned on” Lactose present (acts as inducer starts gene expression) Binds to the repressor protein Repressor changes shapes and detaches from operator RNA pol is not blocked anymore All three enzymes can be produced

10. Operator “turned on” lactose

11. Why is this good? E. coli is able to turn off and on genes when lactose is present/absent Bacteria saves resources and produce only those proteins that are needed

12. Let’s watch it again http://www.youtube.com/watch?v=oBwtxdI1zvk&featu re=relatedhttp://www.youtube.com/watch?v=oBwtxdI1zvk&featu re=related

13. Eukaryotes How is DNA different than Prokaryotes? “junk DNA” ~98% Non-coding Operons not found very often Gene expression occurs at the level of the individual chromosome

14. Introns: “non-coding sections” – are transcribed but not translated ~ 98% of genome Exons: “coding sections” –are transcribed and translated ~2% of genome (23,688 human genes)

15. Modification of RNA Transcription: both introns and exons are transcribed: pre-mRNA Introns are removed and exons are spliced (joined) together Result: mRNA only with exons (coding regions) What spliced the DNA?

16. snRNPs Small nuclear ribonucleoproteins Composed of a small protein molecule and RNA Pronounced “snurps” 60-300 nucleotides Also called “spliceosomes” responsible for pre-mRNA splicing Beginning and ends of introns are recognized and removed At least 4 different kinds of snRNPs Main ones (U1, U2, U4&U6, U5)

18. Alternative splicing Shuffle exons Produce alternative ribonucleotide arrangements Produces different proteins (isoform proteins) Synthesis greater variation of proteins

19. What about the introns? Perhaps not just “junk” Regulation functions and Structural purposes "the cell puts a huge amount of its energy into the creation of these introns, then discards them... Nature would not go to all that trouble without a reason." –C.C. Kopezynski and M. A. T. Muskavitch "a complex mix of different DNA, much of which are vital to the life of the cell." –Nowak At least a dozen studies have found evidence that introns are either directly or indirectly involved in cancer causation. “..at least some introns, and possibly other noncoding DNA, may be involved in DNA packaging in eukaryotes” –Marculis and Sagan

20. Control at Transcription Transcription Factors: regulatory proteins –Help in the placement of RNA pol at the promoter Enhancers: (located far away..upstream or downstream) stimulates transcription –Pg 222

21. Cell differentiation: development of cells that have specialized functions

22. Homeotic Genes Guide the emergence of shape and form Drosophilia (fruit fly) Homeobox: Specific 180nb DNA sequence within a homeotic gene

23. Mutation in Homeobox

24. Cancer Four changes 1.Immortalization: indefinite growth and replication 2.Transformation: becomes independent of factors needed for cell growth 3.Angiogenesis: recruit vascular supply 4.Metastasis: cells dissociate from origin and begin invading normal tissue

25. Angiogenesis

26. Pathways of mutation Need to accumulate mutations in 6 pathways Cells die after about 60 division Telomeres (caps) on end of chromosome –Get smaller and smaller –Suicide (apoptosis) Tumor cells-telomerase-puts caps back on (live forever) Cytochrome c in mitochondria Involved in cell suicide (apoptosis)

27. Oncogenes: mutation of proto-oncogene (regulate cell growth and division) Gene that causes uncontrolled cell proliferation May lead to over expression of proteins Over 100 oncogenes identified

29. Tumor-suppressor genes Act as “brakes” ~30 identified Slow cell division, repair DNA mistakes, tell cells when to die (apoptosis) Can lead to cancer when don’t function properly Abnormalities can be inherited as well as acquired (oncogenes:mutations)

30. Carcinogens Substance that can induce or promote cancer Most are mutagens Chemicals in tobacco smoke, asbestos, radiation, UV Viruses can also cause cancer HPV

31. Types of Cancer Carcinomas: grow in the skin and tissues that line organs Sarcomas: grow in bone and muscle tissue Lymphomas: grow in the lymphatic system Leukemia: uncontrolled production of white blood cells