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Nucleic Acids: Cell Overview and Core Topics

Nucleic Acids: Cell Overview and Core Topics. Outline Cellular Overview Anatomy of the Nucleic Acids Building blocks Structure (DNA, RNA ) Looking at the Central Dogma DNA Replication RNA Transcription Protein Synthesis. DNA and RNA in the Cell. Cellular Overview.

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Nucleic Acids: Cell Overview and Core Topics

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  1. Nucleic Acids: Cell Overview and Core Topics

  2. Outline • Cellular Overview • Anatomy of the Nucleic Acids • Building blocks • Structure (DNA, RNA) • Looking at the Central Dogma • DNA Replication • RNA Transcription • Protein Synthesis

  3. DNA and RNA in the Cell Cellular Overview

  4. Classes of Nucleic Acids: DNA • DNA is usually found in the nucleus • Small amounts are also found in: • mitochondria of eukaryotes • chloroplasts of plants • Packing of DNA: • 2-3 meters long • histones • genome = complete collection of hereditary information of an organism

  5. Classes of Nucleic Acids: RNA FOUR TYPES OF RNA • mRNA - Messenger RNA• tRNA - Transfer RNA• rRNA - Ribosomal RNA• snRNA - Small nuclear RNA

  6. THE BUILDING BLOCKS Anatomy of Nucleic Acids

  7. Nucleic acids are linear polymers. Each monomer nucleotide consists of: 1. a sugar 2. a phosphate 3. a nitrogenous base

  8. Nitrogenous Bases

  9. Nitrogenous Bases DNA (deoxyribonucleic acid): adenine (A) guanine (G) cytosine (C) thymine (T) Why ? RNA (ribonucleic acid): adenine (A) guanine (G) cytosine (C) uracil (U)

  10. Properties of purines and pyrimidines: • keto – enoltautomerism • strong UV absorbance

  11. Pentose Sugars of Nucleic Acids This difference in structure affects secondary structure and stability. Which is more stable?

  12. Nucleosides linkage of a base and a sugar.

  13. Nucleotides - nucleoside + phosphate - monomers of nucleic acids - NA are formed by 3’-to-5’ phosphodiester linkages

  14. Shorthand notation: • sequence is read from 5’ to 3’ • corresponds to the N to C terminal of proteins

  15. DNA Nucleic Acids: Structure

  16. Primary Structure • nucleotide sequences

  17. Secondary Structure DNA Double Helix • Maurice Wilkins and Rosalind Franklin • James Watson and Francis Crick • Features: • two helical polynucleotides coiled around an axis • chains run in opposite directions • sugar-phosphate backbone on the outside, bases on the inside • bases nearly perpendicular to the axis • repeats every 34 Å • 10 bases per turn of the helix • diameter of the helix is 20 Å

  18. Double helix stabilized by hydrogen bonds. Which is more stable?

  19. Axial view of DNA

  20. A and B forms are both right-handed double helix. A-DNA has different characteristics from the more common B-DNA.

  21. Z-DNA • left-handed • backbone phosphates zigzag

  22. Comparison Between A, B, and Z DNA: • A-DNA: right-handed, short and broad, 11 bp per turn • B-DNA: right-handed, longer, thinner, 10 bp per turn • Z-DNA: left-handed, longest, thinnest, 12 bp per turn

  23. Major and minor grooves are lined with sequence-specific H-bonding.

  24. Tertiary Structure Supercoiling supercoiledDNA relaxed DNA

  25. Consequences of double helical structure: • 1. Facilitates accurate hereditary information transmission • Reversible melting • melting: dissociation of the double helix • melting temperature (Tm) • hypochromism • annealing

  26. Structure of Single-stranded DNA Stem Loop

  27. RNA Nucleic Acids: Structure

  28. Secondary Structure transfer RNA (tRNA) : Brings amino acids to ribosomes during translation

  29. Transfer RNA • Extensive H-bonding creates four double helical domains, three capped by loops, one by a stem • Only one tRNA structure (alone) is known • Many non-canonical base pairs found in tRNA

  30. ribosomal RNA (rRNA) : Makes up the ribosomes, together with ribosomal proteins. • Ribosomes synthesize proteins • All ribosomes contain large and small subunits • rRNA molecules make up about 2/3 of ribosome • Secondary structure features seem to be conserved, whereas sequence is not • There must be common designs and functions that must be conserved

  31. messenger RNA (mRNA) : Encodes amino acid sequence of a polypeptide

  32. small nuclear RNA (snRNA) :With proteins, forms complexes that are used in RNA processing in eukaryotes. (Not found in prokaryotes.)

  33. DNA Replication, Recombination, and Repair Central Dogma

  34. Central Dogma

  35. DNA Replication – process of producing identical copies of original DNA • strand separation followed by copying of each strand • fixed by base-pairing rules

  36. DNA replication is bidirectional. • involves two replication forks that move in opposite direction

  37. DNA replication requires unwinding of the DNA helix. • expose single-stranded templates • DNA gyrase– acts to overcome torsional stress imposed upon unwinding • helicases– catalyze unwinding of double helix • disrupts H-bonding of the two strands • SSB (single-stranded DNA-binding proteins)– binds to the unwound strands, preventing re-annealing

  38. Primer RNA primes the synthesis of DNA. Primase synthesizes short RNA.

  39. DNA replication is semidiscontinuous • DNA polymerase synthesizes the new DNA strand only in a 5’3’ direction. Dilemma: how is 5’  3’ copied? • The leading strand copies continuously • The lagging strand copies in segments called Okazaki fragments (about 1000 nucleotides at a time) which will then be joined by DNA ligase

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