1. 8-1 Chapter 8 Lecture Outline See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes.

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-2 DNA and the Importance of Proteins Proteins play a crucial role in the life of a cell. – Microtubules, intermediate filaments and microfilaments maintain the shape of the cell. – Enzymes catalyze important reactions. The recipes for proteins are found in the cell’s DNA. – DNA is organized into genes. Each gene is a recipe for a different protein.

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-3 Nucleic Acid Structure and Function DNA accomplishes two things: – Passes genetic information to the next generation – Controls the synthesis of proteins DNA is able to accomplish these things because of its unique structure.

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-4 DNA Structure DNA is a nucleic acid. Nucleic acids – Large polymers made of nucleotides A sugar molecule – Deoxyribose for DNA – Ribose for RNA A phosphate group A nitrogenous base – Adenine – Guanine – Cytosine – Thymine

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-5 DNA Structure DNA is double- stranded. – Held together by hydrogen bonds between the bases – A-T, G-C

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-6 Base Pairing Aids DNA Replication DNA replication – Is the process by which DNA is copied This is done before cell division. Provides the new cells with a copy of the genetic information – Relies on the base-pairing rules

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-7 Base Pairing Aids DNA Replication – Is accomplished by DNA polymerase and other enzymes Helicase binds to DNA and forms a replication bubble by separating the two strands. DNA polymerase builds new DNA strands that will pair with each old DNA strand. – Where there is an A on the old strand, polymerase will add a T to the new strand. When DNA polymerase finishes a segment of new DNA, it checks its work and corrects mistakes if they happen.

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-8 DNA Replication

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-9 Repairing Genetic Information If a mistake is made when building the new strand – The old strand still has the correct information. – This information can be used to correct the new strand.

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-10 The DNA Code The order of bases in the DNA molecules is the genetic information that codes for proteins. – The sequence of nucleotides forms words that are like a recipe for proteins. Each word contains three base letters. – ATGC are the four letters that are used to make the words. – Each three-letter word codes for a specific amino acid. The order of amino acids in the protein is determined by the order of nucleotides in DNA.

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-11 RNA Structure and Function RNA vs. DNA – RNA has ribose sugar (DNA has deoxyribose). – RNA contains the bases Adenine Guanine Cytosine Uracil (DNA has thymine)

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-12 DNA vs. RNA – RNA’s, like DNA’s, base sequence carries information. – RNA is made in the nucleus and transported to the cytoplasm (DNA stays in the nucleus). – The protein coding information in RNA comes from DNA. – Like DNA replication, RNA synthesis follows the base- pairing rules (A-U; G-C). – RNA is typically single-stranded (DNA is typically double- stranded). – Three types of RNA participate in protein synthesis mRNA tRNA rRNA

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-13 Protein Synthesis The sequence of nucleotides in a gene dictates the order of amino acids in a protein. Before a protein can be made – The information in DNA must be copied into RNA. – This process is called transcription. The information in the RNA can then be used to make the protein. – This process is called translation.

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-14 Transcription During transcription – DNA is used as a template to make RNA – Accomplished by RNA polymerase and follows the base-pairing rules The process of transcription – Occurs in the nucleus – RNA polymerase separates the two strands of DNA. – Only one of the two strands will be used to create the RNA. The coding strand The other DNA strand is called the non-coding strand.

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-15 Transcription of an RNA Molecule

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-16 The Process of Transcription – Only a segment of the DNA strand will be used to create each RNA. These segments are called genes. Each gene starts with a promoter. – The RNA polymerase binds to the promoter to start building an RNA strand. Each gene ends with a terminator sequence. – The RNA polymerase will stop transcribing at the terminator sequence.

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-17 Translation Three types of RNA participate in translation. – mRNA carries the recipe for making the protein. – tRNA and rRNA are used to read the recipe and build the amino acid chain. Codons are sets of three nucleotides that code for specific amino acids. – tRNA reads the codons and brings the correct amino acids.

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-18 The Genetic Code

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-19 Translation Ribosomes are organelles that build proteins. – rRNA is found in ribosomes. – mRNA is read on ribosomes. – Ribosomes are found in two places in the cell. Free-floating in the cytoplasm Bound to the endoplasmic reticulum

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-20 Translation Initiation Translation begins when – The small ribosomal subunit binds to the beginning of the mRNA and searches for the AUG start codon. – At this point, a tRNA brings the first amino acid. The anticodon in the tRNA matches with a codon on the mRNA. Each tRNA carries a specific amino acid based on its anticodon. The start codon, AUG, binds to a tRNA that carries a methionine. – Finally, the large ribosomal subunit joins the complex and the next step, translation elongation, can proceed.

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-21 Initiation

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-22 Translation Elongation The next tRNA binds with the next codon on the mRNA. The ribosome adds this amino acid to the growing polypeptide. The ribosome then moves down to the next codon. The process repeats itself. For each step, a new amino acid is added to the growing protein.

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-23 Elongation

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-24 Translation Termination Elongation continues until the ribosome encounters a stop codon. – UAA, UAG, UGA are stop codons. A release factor binds to the stop codon. – This causes the ribosome to release the polypeptide. – The ribosomal subunits separate and release the mRNA. – The mRNA can be translated again by another ribosome.

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-25 Termination

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-26 Summary of Protein Synthesis

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-27 The Genetic Code is Nearly Universal The process of making proteins from the information in DNA is used by nearly all cells. Nearly all organisms studied to date use the same genetic code. Because of this, we are able to use bacteria as factories to make massive amounts of proteins. – Insulin, growth factor, etc.

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-28 Control of Protein Synthesis Gene expression is how the cell makes a protein from the information in a gene. Cell types are different from one another because they express different sets of genes. – Therefore, have different sets of proteins Cells control gene expression in response to different environmental conditions. Cells can alter gene expression – Controls the quantity of a protein – Controls the amino acid sequence of a protein

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-29 Control of Protein Quantity Cells can regulate how much of a given protein is made by – Controlling how much mRNA is available for translation Cells do this in a number of ways: – Regulating how tightly the chromatin is coiled in a certain region The more tightly the chromatin is coiled, the less likely a gene in that region will be transcribed.

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-30 Eukaryotic Genome Packaging

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-31 Control of Protein Quantity – By increasing or decreasing the rate of transcription of the gene by enhancer and silencer regions on the DNA Activation of enhancer regions increases transcription. Activation of silencer regions decreases transcription. – Through the binding of transcription factors, These proteins bind to the promoter and facilitate RNA polymerase binding and transcription. – By limiting the amount of time the mRNA exists in the cytoplasm, Some mRNA molecules are more stable and will exist longer in the cytoplasm, yielding more protein.

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-32 Different Proteins from One Gene Eukaryotic cells can use one gene to make more than one protein. – In eukaryotic genes, non-coding sequences called introns, are scattered throughout the sequence. After transcription, the introns must be cut out and the coding regions, called exons, must be put back together. – This is called splicing.

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-33 Transcription of mRNA in Eukaryotic Cells

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-34 Alternative Splicing Different combinations of exons from a single gene can be joined to build a number of different mRNAs for a number of different proteins.

35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-35 Mutations and Protein Synthesis A mutation is any change in the DNA sequence of an organism. Can be caused by mistakes in DNA replication Can be caused by external factors – Carcinogens, radiation, drugs, viral infections Only mutations in coding regions of gene will change the proteins themselves.

36. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-36 Point Mutations ̶ a Change in a Single Nucleotide of the DNA Sequence Three types: A nonsense mutation changes a codon to a stop codon. – This causes the ribosome to stop translation prematurely. – CAA (Gln) to UAA (stop) A missense mutation causes a change in the type of amino acid added to a polypeptide. – This may change the way in which a protein functions. – UUU (Phe) to GUU (Val) A silent mutation does not cause a change in the amino acid sequence. – UUU to UUC; both code for Phe

37. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-37 Point Mutations

38. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-38 Sickle Cell Anemia Results from a missense mutation in the gene for hemoglobin – GAA to GUA – Glutamic acid to valine change – Causes the hemoglobin protein to change shape – The molecules stick together in low oxygen conditions. Get stuck in blood vessels, causing the vessels to break apart easily, leading to anemia Also causes blood vessels to clog, preventing oxygen delivery to tissues, which results in tissue damage Causes weakness, brain damage, painful joints, etc.

39. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-39 Normal and Sickled Red Blood Cells

40. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-40 Insertions and Deletions An insertion mutation occurs when one or more nucleotides is added to the normal DNA sequence. A deletion mutation occurs when one or more nucleotides is removed from the normal DNA sequence. Insertions and deletions cause a frameshift. – Ribosomes will read the wrong set of three nucleotides. – Changes the amino acid sequence dramatically – Changes the function of the protein dramatically

41. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-41 Frameshift

42. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-42 Mutations Caused by Viruses Viruses can insert their genetic material into the DNA of the host cell. The presence of the viral material may interfere with the host cell’s ability to use the genetic material in that area because of this insertion. Insertion of human papillomavirus (HPV) causes an increased risk of cancer.

43. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8-43 Chromosomal Aberrations Involves a major change in DNA at the level of the chromosome – Inversions occur when a chromosome breaks, and the broken piece becomes reattached in the wrong orientation. – A translocation occurs when the broken segment becomes integrated into a different chromosome. – A duplication occurs when a segment of a chromosome is replicated and attached to the original segment in sequence. – A deletion occurs when a broken piece is lost or destroyed. All of these effect many genes, thus many proteins. In humans, these mutations may cause problems with fetal development.