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The Central Teaching of Molecular Biology • Information flows from DNA to RNA to PROTEIN DNA Translation RNA Construction Transcription Blue Print PROTEIN 1DNA 1-DNA 2- Synthesis of mRNA in the nucleus Nucleus Transcription 3- mRNA Cytoplasm Nucleus Cytoplasm 4- Movement of mRNA into cytoplasm via nuclear pore mRNA Ribosome 5- Synthesis of Protein 6- Polypeptide Translation The Genetic Code & Nucleic Acids • DNA and RNA are called Nucleic Acids. • Nucleic Acids store information in the form of a molecular language. • The language or code that is written into and read from Nucleic Acids is called the genetic code. Historical Moments in the Discovery of Nucleic Structure Between 1949 and 1953, Erwin Chargaff analyzed the nucleotide base compositions of DNA molecules found in human beings and a number of other organisms as well. The four nitrogenous bases in DNA are adenine (A) O NH2 H N H O N Purine H bases H3C N N thymine (T) N H N H O NH2 H N N H Pyrimidine bases H N H N H N H guanine (G) NH2 O N H H cytosine (C) A T C G What conclusions could you make from Chargaff’s Data? Historical Moments in the Discovery of Nucleic Structure In 1950, after analyzing the data, Erwin Chargaff reported that even though the DNA composition varied from one species to another he suggested that there was a pairing of complementary nucleotide bases (A to T and G to C) in the DNA molecule. Historical Moments in the Discovery of Nucleic Structure Between 1948 and 1952, Linus Pauling discovered the role hydrogen bonding played in the complex helical structure of polypeptides and proteins. His structural discovery, called the “alpha-helix” earned him the Nobel Prize for Chemistry for his work on molecular bonding and structure, especially in proteins. Polypeptide Hydrogen Bonds alpha-helix Protein Historical Moments in the Discovery of Nucleic Structure Between 1950 and 1953, Rosalind Franklin and Maurice Wilkins took x-ray crystallographs (a form of microscopic photography) that showed that the mysterious molecule DNA had a spiral shape. They were awarded Nobel Laureates for their efforts. Twin Scaffolding Sugar Spirals Center Vertical Axis Paired Bases Historical Moments in the Discovery of Nucleic Structure In 1953, James Watson & Francis Crick put all the pieces of “scientific data” together and unscrambled the complex chemical structure of DNA for which they also were awarded Nobel Laureates. Watson & Crick’s DNA Model • Pairing of complementary nucleotide bases Chargaff • Base pairs combine using hydrogen bonds Pauling • The DNA molecule has a spiral shape Franklin & Wilkins • The spiral is a double alpha-helix Pauling End of Introduction to the Central Dogma of Biology Beginning of the Structure of Nucleic Acids and DNA Nucleic Acids are Polymers •A polymer is a large molecule consisting of up to millions of repeated linked molecular units that are relatively light and simple. •Each simple molecular unit is called a monomer U T P Ds DNA monomer P Rs RNA monomer Nucleic Acids are Polymers • Monomeric units are made up of an information carrying nitrogen Base • a sugar Scaffold to hold the base • a phosphate Connector Base Scaffold Rs Ds Connector P • Nucleic acids (DNA and RNA) are composed of 4 different nitrogenous bases O NH2 H N A N N H N H N O N H H NH2 H N H N N C H N T H O G H3C N H purines NH2 O N H H pyrimidines •Each have H bond donors and acceptors O NH2 H N A N N H N H N O N H H NH2 H N H N N C H N T H O G H3C N H purines NH2 O N H H pyrimidines •A-T base pairs form 2 H bonds & G-C base pairs form 3 H bonds O NH2 H N A N N H N H N O N H H NH2 H N H N N C H N T H O G H3C N H purines NH2 O N H H pyrimidines • In RNA the base Thymine (T) is replaced by Uracil (U) NH2 N A U T N H N H N H NH2 O H N G H N N C H N N NH2 H O N H H purines pyrimidines In DNA the scaffold is 2’-deoxyribose, a pentose (five carbon) sugar In RNA the scaffold is ribose, a pentose (five carbon) sugar 5’ 5’ O OHCH2 4’ H H 3’ OH OH 1’ H H 2’ H O OHCH2 4’ H H 3’ OH OH 1’ H H 2’ OH In both DNA and RNA the base is connected to the 1’ position of the scaffolding sugar * O H O H 3C N N H O 5’ OHCH2 4’ H H 3’ OH OH 1’ H H 2’ H * (liberating water - dehydration synthesis) H In both DNA and RNA a phosphate connector is O added to the 5’ position H of the scaffolding sugar N O 5’ O- P O OHCH2 4’ OH H 3’ OH O O N O 1’ H H 2’ H H 3C H nucleoside A nucleoside is the chemical combination of base and sugar. O 5’ O- P O CH2 4’ OH H 3’ OH O H O O H 3C N N O 1’ H H 2’ H H nucleotide O A nucleotide is the chemical combination H N of base, sugar and phosphate. O N O 5’ O O- P O CH2 4’ OH H 3’ OH O 1’ H H 2’ H H 3C H 5’ O The backbone of a OH O nucleic acid 4’is created1’ by connecting H the HH N H phosphate of H this 2’ 3’ monomer to the 3’ H OH O N position of O 5’ O another O- P O CH2 O 1’ 4’ monomer’s OH scaffolding sugar. H H H 2’ 3’ “From 5’C to 3’C” H OH H3C H Nucleotides 3’C are added 5’C in the 5’ to 3’ direction DNA in 3-D Phosphate connectors, Right-hand strand 3’ to 5’ Phosphate connectors, Left-hand strand 5’ to 3’ Scaffolding Sugar & Base “nucleoside” End of the Structure of Nucleic Acids and DNA Beginning of DNA Replication DNA: genes on chromosomes 5’ 3’ The DNA strand opens and will add nucleotides. G to C and T to A. One strand grows continuously, the other grows discontinuously. Enzymes join the strands. 3’ 5’ 3’ 5’ DNA Replication (inside the nucleus) “Parental” DNA DNA Helicase “Parental” DNA with a replication fork DNA Polymerase End of DNA Replication Beginning of RNA Replication (Transcription) DNA produces Protein in two steps Transcription: mRNA production Translation: protein production Transcription of mRNA from DNA “Parental” DNA RNA Polymerase Transcription ~ mRNA Synthesis Single stranded mRNA DNA coding sequence DNA RNA coding sequence RNA INITATION of Transcription GENE INITATION of Transcription Elongation Phase INITATION of Transcription Termination Phase INITATION of Transcription Multiple mRNA Copies During Transcription mRNA code is produced from DNA. GGG CCC TTT AAA CCC GGG AAA UUU To decode DNA into these base What areRNA theuse base combinations A-U, T-A, G-C, C-G code combinations? Decode the DNA sequence below into mRNA ATA TAT GCG GCC GAG TCA TAA UAU AUA CGC CGG CUC AGU AUU rRNA ~ Ribosomal RNA Eukaryotic Ribosome 5,080 RNA base (in 2 or 3 molecules) ~ 49 embedded proteins 1,900 RNA base (in a single molecule) ~ 33 embedded proteins tRNA ~ Transfer RNA Anticodon mRNA Binding Site Amino Acid Accepting End End of mRNA Transcription Beginning of Protein Synthesis (Translation) DNA produces Protein in two steps Transcription: mRNA production Translation: protein production From DNA to RNA to Protein DNA coding sequence A- Inside thesequence nucleus RNA coding mRNA B- In the Cytosol C- At to Ribosome Base Triplets form the Genetic Code The “code words” in DNA and RNA are composed of three contiguous nucleotide bases called a triplets or CODONs. Original DNA GACGACGACGACGAC Base Sequence GUCGUCGUCGUCGUC Translated mRNA Base Sequence Remember! RNA substitutes U for T The DNA triplets which determine the mRNA codons ... code for amino acids at the ribosome... during translation. tRNA with and amino acid in “tow” tRNA’s... have an “anti-codon”... that matches the mRNA’s “codon”. Each of the 20 essential amino acidsmRNA has it’s own special tRNA’s carriers. tRNA mRNA Translation At the ribosome... an mRNA mRNA arrives...and tRNA’s begin to tRNA bring their amino acids... tRNA Protein anti-codons match up with mRNA codons... bonds form between the amino acids. UUU AAA CCC GGG CCC GGG AUU AAA UUU GGG CCC GGG CCC UAA The tRNA’s disengage … | | | | | | | Phe Lys Pro Gly Pro Gly Ile … and the result is a “preprotein” polypeptide chain. Video End of Protein Synthesis (Translation) Beginning of Extra Slides concerning DNA and RNA How is RNA different than DNA? •Ribose Sugar •Uracil for Thymine •Single strand •not self replicating •found all over the cell • Nucleolus - Site of ribosome production • Nucleus - location of DNA, cell organizer • Chromosomes - coiled chromatin • Chromatin - DNA and proteins not coiled • DNA - helix shaped molecule with base sequences that make up the genetic code • RNA - made by DNA, assists DNA to make proteins as a messenger (mRNA), transfer molecule (tRNA) and ribosomal RNA (rRNA). major groove minor groove DNA DNA protein differences between DNA and RNA DNA RNA • deoxyribonucleic acid • no hydroxyl on 2’ sugar • ribonucleic acid • hydroxyl on 2’ sugar • A, C, G, T • thymine has methyl group (CH3) • A, C, G, U • uracil has a hydrogen atom at position 5 • double stranded • single stranded or double stranded • synthesized in 5’ -> 3’ direction • synthesized in 5’ -> 3’ direction Information content of various organisms Organism Millions of bp (base pairs) of DNA Human (Homo sapiens) 3000 Yeast (Saccharomyces cerevisiae) 12 Protist (Amoeba dubia) 600000 Bacterium (Mycoplasma genetalium) 0.5 other biological uses for nucleotides/nucleosides Intracellular communication: • cyclic adenosine monophosphate (cAMP) is a common chemical signalling molecule. Caffeine interferes with cAMP signalling • guanosine triphosphate (GTP) and guanosine diphosphate (GDP) are used by a class of signalling proteins in the cell. The on/off switch is determined by what molecule is bound Energy: • adenosine triphosphate (ATP) is the energy currency of the cell • energy is stored in the covalent bonds which link the three phosphates NH2 N NH2 O N H N N H N N CH2O OH O P O N H N NH2 O O caffeine • mimics the effect of cAMP • a nucleoside triphosphate is the used to build up the polymer • two phosphates are liberated (pyrophosphate) when the next nucleotide is added • this chemical reaction is energetically favorable ATP (adenosine triphosphate) remember, for DNA, dATP is used ATP is also the energy molecule of the cell