Lecture 7 Biological Macromolecules: Nucleic Acids & Central Dogma PDF

Learning outcomes: Functions of nucleic acids Structural unit – the nucleotide of DNA or RNA (compare & contrast); nucleotide vs. nucleoside DNA polymerization - explain: Lecture 7...

Learning outcomes: Functions of nucleic acids Structural unit – the nucleotide of DNA or RNA (compare & contrast); nucleotide vs. nucleoside DNA polymerization - explain: Lecture 7 Phosphodiester bonds Biological dNMPn + dNTP à dNMPn+1 + PPi macromolecules Nucleic acid is made from 5” to 3” direction Compare and contrast DNA vs. RNA Nucleic Acids & Complementarity of base pairing Central Dogma Describe the 4 structural levels of nucleic acids Scientists who discovered the structure of DNA The Central Dogma How is DNA used to estimate evolutionary relationships Special types of nucleotides and their function Nucleic acids – store genetic information 2 RNAs DNA DNA = deoxyribonucleic acid Bacteria Plasmids Archaea Eukaryotes HIV virus Some viruses Varicella-zoster (chickenpox) E. coli HPV (warts & cervical cancer) RNA = ribonucleic acid some viruses Influenza Poliovirus HIV Eukaryotic cell Nucleic acids – transmit information and regulate gene expression How a cell makes proteins? Information flows from DNA (genes) to RNA to protein Information flows from DNA to RNA RNA rRNA in a ribosome (proteins in blue, RNA in orange) (rRNAs; mRNAs; tRNAs; siRNAs; snRNA) Transcription Folding How a cell regulates which proteins are made? Small RNAs (cell differentiation & development) Prevents translation (making a protein) Nucleic acids are polymers of nucleotides Nucleic acids are polymers of nucleotides Sugar pentose R=OH : ribose R=H: deoxyribose Nucleoside monophosphate Nucleoside diphosphate Nucleoside triphosphate Nucleotides polymerize via phosphodiester linkages RNA polymerization Condensation reaction Phosphodiester linkage DNA polymerase 3’-end 5’-end Nucleic acid polymerization – a new nucleotide is added to the 3’ end of the newly made strand Catalyzed by DNA or RNA polymerase DNA polymerization: ➖dNMPn + dNTP ➖dNMPn+1 + PPi −dTMP dCTP PPi −dCMP Nucleic strand “grows” in 5’ to 3’ direction  DNA and RNA differ DNA vs. RNA RNA DNA Single Double stranded stranded Ribose Deoxyribose Uracil Thymine Shorter Longer Figure adapted from Nat. Human Res. Inst. In a double stranded nucleic acid, bases pair by hydrogen bonding between nucleotides Complementary base pairing Nucleotide Base Pairing in dsDNA: Nucleotide Base Pairing in dsRNA: A pairs with T (via 2 H-bonds) A pairs with U (via 2 H-bonds) C pairs with G (via 3 H-bonds) DNA The two strands of dsDNA run antiparallel. RNA single stranded RNA (ssRNA) OH Secondary structure of RNA OH Stem (dsRNA) OH Loop (ssRNA) Structure of a nucleic acid Primary structure – linear sequence of nucleotides (nitrogenous bases) along the Stem Stem & loop strand of DNA or RNA Pseudoknot Secondary structure – Stems, loops, pseudonots Helices Tertiary structure(3D) - helices Quaternary structure – chromatin (DNA & histones); RNAs interacting in ribosomes or spliceosomes DNA around histones (nucleosome) Structure of a nucleic acid Primary structure – linear sequence of nucleotides (nitrogenous bases) along the strand of DNA or RNA Secondary structure – Stems, loops, pseudonots Tertiary structure(3D) - helices Quaternary structure – chromatin (DNA & histones); RNAs interacting in ribosomes or spliceosomes Discovery of DNA structure DNA is a molecule Base pairs X-ray crystallography uncovering of heredity complementarity helical structure of DNA Oswald Avery Erwin Chargaff Rosalind Franklin Maurice Wilkins (1877-1955) (1905-2002) (1920-1958) (1916-2004) DNA helix; DNA strand are antiparallel; hypothesis for DNA replication Photo 51 Double helix James Watson (1928-) Sugar-phosphate backbone Francis Crick (1916-2004) Bases protruding inside the helix Strands antiparallel  Concept check: Your instructor gives one dsDNA sequence to you and another to your partner and mentions that both DNA sequences are of the same length (in terms of base pairs) and both contain 30% A. What would be the percent of the remaining bases (C, G, and T) in these sequences? C is 20%, G is 20%, and T is 30% Would the sequence of bases in the DNA that you received be the same as the one your partner received? Explain your answer. It might be different (bases may be arranged in different permutations and combinations).  Concept check: What will happen when a purified DNA is heated to 94°C? The Central Dogma: DNA carries information that is expressed through RNA DNA mRNA Protein TRANSCRIPTION TRANSLATION DNA REPLICATION mRNA Semiconservative DNA replication Messenger RNA (mRNA) is complementary (cell division) to DNA strand coding for protein.  The DNA base sequence reveals evolutionary relationships Gibbon Nomascus leucogenys Coquerel’s sifaka Propithecus coquereli Walrus Chimpanzee Odobenus rosmarus Pan troglodytes Grey mouse lemur Microcebus murinus Crab-eating macaque Macaca fascicularis Rhesus Macaque Macaca mulatta Partial mRNA for insulin: The DNA base sequence reveals evolutionary relationships 0.73 Macaca_fascicularis Chimpanzee Macaca_mulatta 0.49 Gibbon 0.95 Homo_sapiens 0.93 Pan_troglodytes Nomascus_leucogenys Coquerel’s sifaka 0.95 Propithecus_coquereli Grey mouse lemur Microcebus_murinus Walrus Odobenus_rosmarus Tree based on mRNA for insulin 0.07 Nucleotides have other important functions ATP = adenosine triphosphate; energy “currency” of the cell GTP = guanosine triphosphate; energy source in protein synthesis; signaling pathways cAMP = cyclic adenosine monophosphate many functions in the cell: signaling (hormones), gene expression, transmission of nervous stimulus