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Biochemistry

Biochemistry

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Biochemistry

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  1. Biochemistry Chapter 25 Nucleotides, Nucleic Acids, and Heredity

  2. Problem Sets • PS #1 • Sections 25.1 – 25.3 • # 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 19, 20, 21, 22, 23, 25, 27, 29, 30, 31, 32, 33 • PS #2 • Sections 25.4 – 25.8 • # 37, 38, 39, 41, 44, 45, 48, 50, 54, 59, 62, 63, 65, 70, 75, 90, 91, 94

  3. 25.1 The Molecules of Heredity • Heredity • The transfer of anatomical and biochemical characteristics from one generation to another • The Cell Nucleus • Chromosomes – structures that control heredity • Genes – basic components of heredity • Each gene controls the production of a protein • Genetic information is contained in compounds called nucleic acids

  4. 25.2 Nucleic Acids • DNA (deoxyribonucleic acid) • Found in chromosomes • RNA (ribonucleic acid) • Found outside of chromosomes • Each has its own specific function • DNA and RNA are polymers • Nucleotides – building blocks (monomers) • Each nucleotide is made up of a base, a monosaccharide, and a phosphate

  5. 25.2 Nucleotide Bases Heterocyclic aromatic amines built from purine and pyrimidine Presence of amine group makes them basic Highlighted hydrogen is lost when bonding to monosaccharide Thymine is only found in DNA, Uracil is only found in RNA

  6. 25.2 Sugars b-2-Deoxy-D-ribose b-D-Ribose Nucleoside – sugar plus base Linked through a C-1 b-N-glycosidic bond

  7. 25.2 Formation of Nucleosides

  8. 25.2 Phosphate C-5 of a nucleoside will form an ester with phosphoric acid Nucleotide – nucleoside combined with one to three phosphates Nucleoside = base + sugar Nucleotide = base + sugar + phosphate Nucleic acid = a chain of nucleotides Adenosine 5’-triphosphate (ATP)

  9. 25.2 Nucleosides and Nucleotides

  10. 25.3 Primary Structure of DNA and RNA • Sequence of nucleotides • Backbone • Alternating sugar and phosphate • Phosphate is linked to 3’ carbon of one sugar and 5’ carbon of next • 3’ end and 5’ end • Order of bases • Always begin at 5’ terminus • Ex: -ATTGAC-

  11. Base Sugar Phosphate 5’ terminus Blue H’s are ionized at neutral pH 3’ terminus

  12. 25.3 Secondary Structure of DNA • Watson and Crick (1953) • Double helix • Right-handed helix • Two nucleotide chains run antiparallel • One runs 5’ to 3’, the other runs 3’ to 5’ • Sugar-phosphate backbone is outside • Hydrophobic bases inside • Complementary base pairs held together by hydrogen bonding

  13. A freely-rotating strand of B DNA Note the major and minor grooves become visible as the molecule rotates Can you locate the 3’ and 5’ terminus ends?

  14. Correct pairing of nucleotide bases Always pair one purine with one pyrimidine Note the plentiful opportunities for hydrogen bonding

  15. Incorrect pairing of nucleotide bases Fewer opportunities to hydrogen bond Also, bases will not stack properly if two purines are paired

  16. 25.3 Higher-Order Structures of DNA • DNA molecules are coiled around basic proteins called histones • Acidic DNA and basic histone held together by electrostatic attraction • Nucleosomes • 8 histone molecule core • 147 base-pair DNA helix wrapped around core • Chromatin • 30 nm wide fibers • Nucleosomes wrapped in a solenoid structure

  17. 25.3 Differences Between DNA and RNA • Different bases • DNA uses A, G, C, T • RNA uses A, G, C, U • Different sugar • DNA uses 2-deoxy-D-ribose • RNA uses D-ribose • Different structure • DNA is a double helix • RNA is usually a single strand (there are 6 types)

  18. 25.4 Messenger RNA (mRNA) • mRNA is produced during transcription • Genetic information is copied from DNA to mRNA • mRNA carries information to the cytoplasm • mRNA is a single strand • Base sequence is the complement of the DNA strand that was copied • Length is roughly 750 nucleotides • Acts as a template for protein synthesis • Degraded when no longer needed

  19. 25.4 Transfer RNA (tRNA) • Small RNA strand • 73 – 93 nucleotides • Transports amino acids to mRNA for protein synthesis • Different one foreach amino acid • 3’ end attaches to amino acid • Anticodon loop fits onto the mRNA template

  20. 25.4 Other Classes of RNA • Ribosomal RNA (rRNA) • Ribosomes are the site of protein synthesis • Composed of proteins and rRNA molecules • Small Nuclear RNA (snRNA) • Processes mRNA into a mature form in the nucleus of eukaryotes • Micro RNA (miRNA) • Important in timing an organism’s development • Small Interfering RNA (siRNA) • Controls gene expression

  21. 25.5 Genes • A gene is a stretch of DNA a few hundred nucleotides long that codes for one protein • Each DNA molecule holds many genes • In bacteria genes are contiguous, in higher organisms they are not • Exons – coding sequences • Introns – noncoding sequences • Satellites • short sequences repeated hundreds of times • Provide stability for chromosomes

  22. 25.6 DNA Replication • Replication • process by which DNA copies itself during cell division • Process must be error free • A change in one nucleotide changes the entire protein the gene codes for • Origin of replication • Point at which replication can begin • Each chromosome has several hundred origin points where replication can occur simultaneously

  23. 25.6 DNA Replication • Replication fork • Point on the DNA strand where the double helix is unwound and replication is proceeding • Replication can only happen 5’  3’ • Leading strand • The 5’3’ strand; replicated continuously • Lagging strand • The 3’5’ strand; replicated discontinuously • Primer – RNA strand that starts replication

  24. 25.6 Steps in DNA Replication • Opening of the superstructure • Unwinding of condensed chromosome structure • Relaxation of higher-order structures • Performed by gyrases • Opens up the supercoiled structure of DNA • Unwinding of the double helix • Performed by helicases • Placing of primers / primases • Short RNA strands needed to start replication

  25. 25.6 Steps in DNA Replication • DNA polymerization • Performed by DNA polymerases • Brings proper nucleotide to fit parent strand • Joins nucleotides with sugar-phosphate backbone • In the 3’5’ strand, this is done in short fragments • Called Okazaki fragments • Ligation • Performed by DNA ligase • Okazaki fragments are joined together

  26. 25.6 DNA Replication

  27. 25.7 DNA Repair • Mutation – change in base sequence • Errors in copying • Exposure to radiation or oxidizing agents • Base Excision Repair (BER) Pathway • Specific damaged base is removed, along with its sugar-phosphate backbone, and replaced with the correct base by DNA polymerase • Nucleotide Excision Repair (NER) • Several nucleotide sequences replaced

  28. 25.8 Amplification of DNA • Cloning • Organism replicates DNA as it grows • Polymerase Chain Reaction (PCR) • Make millions of copies of specific sequences • Works very quickly • Synthesize primers that fit on the ends of the desired sequence • Primers attach to sequence and start replication • Cycle repeats millions of times