1. Chapter 18

2. Transcription

3.  E. coli’s DNA is tightly coiled so it will fit inside the cell ◦ most of the DNA is found in the nucleoid region  Most bacteria have a number of plasmids ◦ Plasmids are much smaller circles of DNA, each with only a few genes

5. Operon Operon: cluster of related genes with on/off switch Four Parts: 1.Promoter – where RNA polymerase attaches 2.Repressor-blocks polymerase 3.Operator – “on/off”, controls access of RNA poly 4.Genes – code for related enzymes in a pathway

6. Regulatory generepressor Regulatory gene: produces repressor protein that binds to operator to block RNA poly

8.  Normally ON  Anabolic (build organic molecules)  Organic molecule product acts as corepressor  binds to repressor to activate it  Operon is turned OFF trp operon  Ex. trp operon

9. trp operon

10.  Normally OFF  Catabolic (break down food for energy) inducer  Repressor is active  inducer binds to and inactivates repressor  Operon is turned ON lac operon  Ex. lac operon

11. lac operon

12. http://highered.mcgraw- hill.com/sites/0072556781/student_view 0/chapter12/animation_quiz_3.html

13.  Stimulatory protein-catabolite activator protein (CAP), an activator of transcription  When glucose (a preferred food source of E. coli) is scarce, CAP is activated by binding with cyclic AMP  Activated CAP attaches to the promoter of the lac operon and increases the affinity of RNA polymerase-accelerates transcription  When glucose levels increase, CAP detaches from the lac operon, and transcription returns to a normal rate  CAP helps regulate other operons that encode enzymes used in catabolic pathways

14. Fig. 18-5 (b) Lactose present, glucose present (cAMP level low): little lac mRNA synthesized cAMP DNA Inactive lac repressor Allolactose Inactive CAP lac I CAP-binding site Promoter Active CAP Operator lacZ RNA polymerase binds and transcribes Inactive lac repressor lacZ Operator Promoter DNA CAP-binding site lac I RNA polymerase less likely to bind Inactive CAP (a) Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized

15.  http://highered.mcgraw- hill.com/sites/0072556781/student_view0/c hapter12/animation_quiz_4.html http://highered.mcgraw- hill.com/sites/0072556781/student_view0/c hapter12/animation_quiz_4.html

16. Many stages

17.  Typical human cell: only 20% of genes expressed at any given time  Different cell types (with identical genomes) turn on different genes to carry out specific functions differential gene expression  Differences between cell types is due to differential gene expression

19.  Nucleosomes ◦ The DNA double helix wraps around proteins called histones ◦ This gives the appearance of “beads on a string” ◦ The “beads” (nucleosomes) are joined by “string” (linker DNA)

20.  The nucleosomes interact with one another to coil and fold multiple times in a specific conformation ◦ 30-nm fiber ◦ Looped domains ◦ Metaphase chromosomes (most tightly condensed)

21. Chromatin Structure:  Tightly bound DNA less accessible for transcription  DNA methylation: methyl groups added to DNA; tightly packed;  transcription  Histone acetylation: acetyl groups added to histones; loosened;  transcription

23.  The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence  Modifications on chromatin can be passed on to future generations  Unlike DNA mutations, these changes to chromatin can be reversed (de-methylation of DNA)  Explains differences between identical twins

24. Transcription Initiation:  Control elements bind transcription factors  Enhances gene expression

25. Enhancer (distal control elements) Proximal control elements Poly-A signal sequence Termination region Downstream Promoter Upstream DNA Exon Intron Exon Intron Cleaved 3 end of primary transcript Primary RNA transcript Poly-A signal Transcription 5 RNA processing Intron RNA Coding segment mRNA 5 Cap 5 UTR Start codon Stop codon 3 UTR Poly-A tail 3

26. Enhancer promoter activators Enhancer regions bound to promoter region by activators

27. Fig. 18-10 Control elements Enhancer Available activators Albumin gene (b) Lens cell Crystallin gene expressed Available activators LENS CELL NUCLEUS LIVER CELL NUCLEUS Crystallin gene Promoter (a) Liver cell Crystallin gene not expressed Albumin gene expressed Albumin gene not expressed

28.  The life span of mRNA molecules in the cytoplasm is a key to determining protein synthesis  Eukaryotic mRNA is more long lived than prokaryotic mRNA  The mRNA life span is determined in part by sequences in the leader and trailer regions

29. Proteasome and ubiquitin to be recycled Proteasome Protein fragments (peptides) Protein entering a proteasome Ubiquitinated protein Protein to be degraded Ubiquitin Proteasomes-giant protein complexes that bind protein molecules and degrade them The initiation of translation of selected mRNAs can be blocked by regulatory proteins that bind to sequences or structures of the mRNA Regulation of Translation

30. Regulation of mRNA: micro RNAs (miRNAs) small interfering RNAs (siRNAs) micro RNAs (miRNAs) and small interfering RNAs (siRNAs) can bind to mRNA and degrade it or block translation

32.  http://highered.mcgraw- hill.com/olcweb/cgi/pluginpop.cgi?it=swf::53 5::535::/sites/dl/free/0072437316/120080/ bio31.swf::Control%20of%20Gene%20Expressi on%20in%20Eukaryotes http://highered.mcgraw- hill.com/olcweb/cgi/pluginpop.cgi?it=swf::53 5::535::/sites/dl/free/0072437316/120080/ bio31.swf::Control%20of%20Gene%20Expressi on%20in%20Eukaryotes

37. Section 18.4

38. 1. Cell Division: large # identical cells through mitosis 2. Cell Differentiation: cells become specialized in structure & function 3. Morphogenesis: “creation of form” – organism’s shape

40.  Cytoplasmic determinants: maternal substances in egg distributed unevenly in early cells of embryo

41.  Induction: cells triggered to differentiate from neighboring cells  Cell-Cell Signals: molecules produced by one cell influences neighboring cells ◦ Ex. Growth factors

46. Section 18.5

47. 1. Proto-oncogene = stimulates cell division 2. Tumor-suppressor gene = inhibits cell division  Mutations in these genes can lead to cancer

48. Proto-OncogeneOncogene  Gene that stimulates normal cell growth & division  Mutation in proto- oncogene  Cancer-causing gene Effects:  Increase product of proto-oncogene  Increase activity of each protein molecule produced by gene

50.  Ras gene: stimulates cell cycle (proto- oncogene) ◦ Mutations of ras occurs in 30% of cancers  p53 gene: tumor-suppresor gene ◦ Functions: halt cell cycle for DNA repair, turn on DNA repair, activate apoptosis (cell death) ◦ Mutations of p53 in 50+% of cancers

51. Fig. 19.12 Receptor Growth factor G protein GTP Ras GTP Ras Protein kinases (phosphorylation cascade) Transcription factor (activator) DNA Hyperactive Ras protein (product of oncogene) issues signals on its own MUTATION NUCLEUS Gene expression Protein that stimulates the cell cycle (a) Cell cycle–stimulating pathway MUTATION Protein kinases DNA DNA damage in genome Defective or missing transcription factor, such as p53, cannot activate transcription Protein that inhibits the cell cycle Active form of p53 UV light (b) Cell cycle–inhibiting pathway (c) Effects of mutations EFFECTS OF MUTATIONS Cell cycle not inhibited Protein absent Increased cell division Protein overexpressed Cell cycle overstimulated 1 2 3 4 5 2 1 3

52.  Cancer results when mutations accumulate (5- 7 changes in DNA)  Active oncogenes + loss of tumor-suppressor genes  The longer we live, the more likely that cancer might develop

53.  Embryonic development occurs when gene regulation proceeds correctly  Cancer occurs when gene regulation goes awry