Lecture 10Outline of Previous Lecture1. Carbohydrates2. Monosaccharides3. Disaccharides4. PolysaccharidesOutline of Current Lecture1. Nucleic Acids2. Common Enzymes that make or degrade Nucleic Acids3. Why Study nucleic acids?Current Lecture1. Nucleic Acids – Carriers of Biological InformationDNA and RNA bothe are polymers called nucleic acidsBoth built from monomers called nucleotidesDNA – stores genetic data in genome and is polymerized from monomers called deoxyribonucleotides (dATP, dCTP, dGTP, TTP)RNA – is genetic data activated for making proteins and is polymerized from monomers called ribonucleotides (ATP, CTP, GTP, UTP)Linear sequence of bases in DNA and RNA constitute genetic data – instructions to make all specific proteins or to perform various gene regulatory functionsNucleic acids – BasicsCalled nucleic acids because these polymers carry substantial negative charge at neutral pHCalled nucleic acids since these polymers are largely associated with the cell nucleusThe main role of nucleic acids is to specify the phenotype of an organism by directing the production of a particular set of protein productsThree key cellular processes convert genetic information into specific proteinsCentral Dogma – information flowReplication – copying DNA (entire genome) prior to every cell divisionTranscription – coping certain parts of DNA into messenger RNAs (mRNAs) or other RNAsTranslations – convert mRNA information into polypeptides – linear AA sequencesGenetic Code: DNA or RNA base sequence co-linear with polypeptide AA sequenceNonoverlapping base triplets in nucleic acids code for specific amino acidsGenerally only one reading frame activeNucleotide StructureNucleic acids are the polymerized form of nucleotidesJoined together by a phosphodiester linkage between 3’ and 5’ hydroxylsNA chain has polarity distinct 3’ end and 5’ endsBe able to draw polymers in complete atomic detail!***Unexpected nucleic acid property – complemetary base-pairing of A/T and G/CSpecific purine bases form hydrogen bonds with specific pyrimidine bases:G with C – forms 3 hydrogen bonds (more stable bp)G & C don’t base pair in the same geometry with A &TA with T (or U) – forms 2 hydrogen bonds (less stable bp)A & T don’t basepair in the same geometry as G & CWatson/Crick base pairing—specific pattern of hydrogen bonds between basesNumerous non-WC H-bonded pairings are known – alternative base pairs have different dimensionsBase pairing is primary key to nucleic acid function!Be able to draw base pairing! ***Base pairs are virtually same size and shapeAntiparallel duplex helical structureThe base sequence in one strand specifics the base sequence of the complementary strand** be able to derive or recognize complementary sequencesBase pairing is reversible – high temperature or high pH dissociates DNA strands – called melting or denaturationLow temperature or neutral pH favors strand association – annealingThis ability is important for techniques involving hybridizationAssociation with completely separate strands is SLOWBase pairing is main key to nucleic acid structure and function1. Since the base sequence of one strand defines the base sequence of the other strand, essentially 2 copies of genetic information are present in haploid cell – information of one strand can be used to repair or create the other strand2. Base pairing allows one strand to serve as TEMPLATE for synthesis of other strandDNA and RNA – differences in structure and functionDNA – stable form of genetic infoExclusively uses deoxyribose sugarsBases are adenine, cytosine,guanine, and thymineUsually maintained as a double-stranded helixIn most organims, huge linear DNA molecules called chromosomes, each encodes hundreds or thousands of proteins and information to regulate outputRNA – unstable info for protein synthesisExclusively contains ribose sugarsBases are adenine, cytosine, guanine, and uracilT is a methylated form of UUsually functions as short single-stranded but folded species that commonly encodes one protein or performs one taskMany RNAs have guiding regulatory or catalytic functionsDNA duplex: familiar B form helix2 strands – right-handed double helixsugar-phosphate backbone on outside, bases are inside – anhydrous/hydrophobic, edges of the bases interact with the salthydrophobic effect – drives the structure of the chainstacking creates two unequal grooves (major—wider grooze and minor-narrow groove)10.5 bases/turn in solutionRNA: diverse structures & functionsRNAs are usually single-stranded moleculesShort complementary regions within these single strands allow intra-strand base pairing, making complex folded secondary structuresSome contain diverse modified bases or sugars and alternative forms of base pairing are knownBoth RNA and DNA folding are driven by weak interactions – hydrogen bonding, van der waals, release of ordered solvent, minimizing steric clashRNA: different functional classesMessenger RNA (mRNA) – copy of the DNA information needed to make a protein, so there are many types of different mRNAsShort lived, manyTransfer RNA (tRNA) – carry activated amino acids to ribosomes for polypeptides synthesisSmall molecules ~73 to 95 nucleotides longRibosomal RNA (rRNA) – main component of ribosomes, accounts for ~80% of RNA in cellsCatalytic RNA – specific catalytic activities, widespread examples – ribosomes, RNasePRegulatory RNA – riboswitches, miRNAsComplex secondary structures in RNA can serve catalytic functions: Example Bacterial RNase PFound in all bacteria, and eukaryotes (different structures)Catalytic RNACarry out chemical reactionsAlmost globular structureG-U pairing – not the same geometry as W/C pairsAs stable as an A-U pairRNAs often have additional modifications, linkages, alternate types of base pairingExample – tRNAClover structurepolymer5-20 modificationsG-C pairing, hydrogen bonding with other base pairsNucleic Acid Structure: SummaryNucleic acids share a special feature – hydrogen bonds between bases – WC pattern most important – helices form by specific BPsBasepairing makes antiparallel duplex structureDNA – stable duplex molecules – stores genetic codeRNA – major roles is information carrier for generating protein from genetic code stored in DNA2. Common Enzymes that make or degrade Nucleic AcidsPolymerases – Make DNA or RNa from precursors dNTPS or NTPs in usually template-directed reactionDNA