DNA: Structure and Function

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1 DNA: Structure and Function Biology's biggest moment in the 20th century, as heralded in six paragraphs in The New York Times, May 16, Research of DNA Structure Chargaff s Rule of Ratios Amount of adenine always equals thymine Maurice Wilkins research confirmed DNA was a helix Amount of cytosine always equals guanine Amount of A+T together is independent of C+G 3 4 3D Structure of Proteins L. Pauling made the discovery using X-ray crystallography: 3D Structure of Proteins Pauling made paper models to resemble amino acids & assembled them into protein model Tiny bit of crystallized sample is bombarded with X- rays Spots & areas thus formed reveal atomic arrangement in the sample Model looked like twisted helix winding around axis (elongated spiral) Pauling called the model alpha helix Some proteins have a regular structure 5 6

2 7 What is the Structure of DNA? DNA structure must be compatible with its 4 roles: Make copies of itself Dr. Francis Crick, left, and Dr. James D. Watson at Cambridge in the 1950's, after they discovered the double helix. The two have continued to drive the genetic revolution. Dr. Crick, above right, has been at the Salk Institute since Dr. Watson worked at Harvard and is now president of the Cold Spring Harbor Laboratory. Encode information Control cells & tell them what to do Change by mutation 8 DNA is a Double Helix Nucleotides that make up DNA have 3 components: Phosphate group 5-C sugar (deoxyribose) Nitrogen-containing organic base Four Bases of DNA Nucleotides Adenine (A) purine Guanine (G) purine Thymine (T) pyrimidine Cytosine (C) - pyrimidine 9 10 phosphate base = thymine Characteristics of Four Bases sugar Watson & Crick phosphate sugar base = cytosine Assumed that the phosphate group & sugar connect the bases together phosphate Thus, nitrogenous bases could occur in any order without changing basic molecular structure sugar base = adenine Consistent with role as repository of information phosphate sugar base = guanine

3 13 Watson & Crick s Research Watson & Crick s Research Considered there could be 2 helices with adenine on one & thymine on the other Proposed pairing relationships guanine on one & guanine on other Pairing relationship sequence on one chain is complement of sequence on other Used Pauling s model building approach to make a metal model Their model was sugar-phosphate backbone (like rails on ladder), twisted into helix as predicted by pictures 14 Watson & Crick s Research Watson & Crick s Research Paired bases projecting from backbone formed rungs of a ladder projecting from rails & satisfied Chargaff s ratios Found bonds holding nucleotides together were covalent Bonds holding base pairs relatively weak, but many together strong DNA Replication Replication process by which DNA copies itself Precedes cell division Watson & Crick said replication begins when weak bonds connecting parental strands break Strands separate as halves of a zipper DNA Replication Watson & Crick exposed bases attract complementary basess (T pairing with A, C pairing with G, etc.) Each strand acts as a blueprint upon which a new partner is assembled As each new strand forms, nucleotides are lined together to form a complete strand 17 18

4 19 Double Helix of DNA DNA Replication Result is two double-stranded daughter helices Each composed of one parental strand & one newly synthesized strand This mechanism is called semiconservative replication Watson & Crick proposed this solely on basis of logic, no scientific evidence 20 How is Info in DNA Expressed? RNA as an Intermediary A. Garrod, 1902, proposed connection between genes & proteins Proteins amino acid polymers that fold, twist into 3D structures Amino acids differ form each other in side group (R group composition) DNA codes for protein through related polymer of ribonucleic acid nucleotides or RNA DNA that encodes protein is copied into sequence of RNA nucleotides Smaller, more mobile RNA goes to the part of the cell where sequence is decoded into protein The genes determine protein primary structure Decoding DNA: DNA RNA PROTEIN Two separate processes involved: DNA used as the template to make RNA Translation RNA serves as the template for the sequence of amino acids in a protein Structure of RNA Nucleotides & Polynucleotides Composed of phosphate group, nitrogenous base (A, G, C, U [instead of T]) & ribose sugar Nucleotides are joined together into singlestranded molecule by covalent bonds 23 24

5 25 Differences: DNA & RNA They contain different sugars DNA contains deoxyribose RNA contains ribose Nitrogenous bases DNA contains A, G, T, & C RNA contains A, G, U, & C Uracil (U) replaces thymine (T) in RNA, thus A pairs with U when DNA is used as a template to make RNA Differences: DNA & RNA DNA most stable as double helix RNA most often exists as a single strand of nucleotides Size DNA molecules are larger RNAs are smaller Mobility DNAs are basically immobile RNAs are highly mobile Life span DNAs are long-lived RNAs are broken down soon after their job is done 26 Messenger RNA (mrna) carries genetic info from DNA (nucleus) to cytoplasm where it is translated into protein Transfer RNA (trna) is interpreter molecule that brings amino acids to site where mrna translated into protein Ribosomal RNA (rrna) - >80% of RNA in most eukaryotes Several rrnas & many proteins combine to form ribosomes Where translation occurs Enzymes involved in and control transcription The enzyme RNA polymerase catalyzes assembly of RNA & places appropriate complimentary RNA nucleotides into new RNA Other enzymes separate DNA double helix strands to allow transcription 29 30

6 31 What raw materials are required for making RNA? Ribonucleotides A, U, G, C that are the building blocks of RNA A template or blueprint of the final product DNA Fuel to drive the assembly line linking ribonucleotides nucleotide triphosphates Equipment to accomplish actual assembly of the final product from DNA must start & end at specific places on DNA Certain sequences within DNA (promoter sequences) Signal RNA polymerase to attach to template and begin transcribing 32 Translation Proteins are synthesized in translation assembly of protein from mrna template More complex & machinery of translation is far more elaborate than that of transcription Translation What is needed for translation? Raw materials (amino acids) Energy to drive synthesis Template to determine amino acid sequences Machinery to do synthesis Reliable interpreter (trna) Stable synthesis platform (ribosome) Translation Transfer RNAs carrying amino acids The Genetic Code 3 RNA nucleotides code for 1 amino acid The language of genes is written in sequence of nitrogenous base Can be translated 3 at a time into amino acid words 35 36

7 37 The Genetic Code Need code to stand for 20 amino acids Alphabet for code has 4 letters (A, G, C, T or U) Can only make 4 one-letter words (4 1 ), 16 twoletter words (4 2 ), 64 three-letter words (4 3 ) The Genetic Code To code unambiguously for 20 amino acids Need at least 20 words Three-letter words would be the minimum\ M. Nirenberg & H. Matthaei, 1960s, developed a technique for cracking code 38 The Genetic Code Features of code Code is universal, applies to humans & all other living things Most amino acids have 2 and many have 4 triplet codons that code for them

8 43 44 What Makes Cells Different from Each Other? During lifetime A person may manufacture as many as 100,000 different proteins, but Only ~5000 are found in any one cell at any given time What Makes Cells Different from Each Other? Eukaryotes regulate genetic expression at many levels is important in eukaryotes as well but there are other levels of regulation DNA Mutations Mutations are essential for life Mutation is the sudden appearance of a new allele DNA Mutations Some mutations involve whole chromosomes Gene expression is the process of making proteins from DNA nucleotide message Mutations and protein synthesis Polyploidy arises as genetic accident, but can be advantageous Aneuploidy is a change in chromosome number involving single chromosome or single homologous pair 1. Source of mutations a. Errors in replication and transcription b. Exposure to mutagens 2. Changes in DNA can result in changes in encoded proteins 47 48

9 49 DNA Mutations Inversions Piece of chromosome broken, then reincorporated in chromosome in reversed order Deletions DNA Mutations Micromutations that involve single DNA bases or just a few bases Called point mutations Neutral mutations Most mutations are harmful, but Many have little or no impact on recipients Parts of chromosome spontaneously deleted 50 gene (a) gene in DNA (template strand) (a) codon (b) mrna (codons) (b) anticodon (c) trna (anticodons) (c) amino acids (d) (d) protein (amino acids) Gene expression is the process of making proteins from DNA nucleotide message III. Gene expression is the process of making proteins from DNA nucleotide message The effects of mutations a. Insignificant The effects of mutations 1) Some nucleotide substitution mutations 2) Degeneracy of codons a) More than one codon for most amino acids b) Third nucleotide position is often not important e.g., G-U-n = valine; U-C-n = serine; C-G-n = arginine 3) Functional equivalency of amino acids a) Neutral mutations b. Harmful 1) Some nucleotide substitutions 2) Nucleotide insertions or deletions result in frameshifts, null mutations 3) Altered or lost protein function 53 54

10 55 III. Gene expression is the process of making proteins from DNA nucleotide message Mutations and protein synthesis (cont.) 3. The effects of mutations Regulation of gene expression how a gene is turned on and off A. Individual cells express only a small fraction of their genes c. Beneficial 1) Altered protein function is a source of genetic variation 2) Significance to ability to evolve B. Gene expression is influenced by developmental stage and environment 56 Regulation of gene expression how a gene is turned on and off Types of regulation 1. Rate of transcription or translation 2. Rate of enzyme activity IV. Regulation of gene expression how a gene is turned on and off Regulation involves signaling molecules 1. The albumin gene, estrogen, and the estrogen receptor The Cell Cycle Mitosis and meiosis are single steps in cell cycle The Cell Cycle Cells not in process of dividing are in interphase Chromosomes are duplicated in preparation for the next round of division during interphase 59 60

11 61 Control of the Cell Cycle The cell cycle is highly regulated If a cell breaks free of its parent organ It starts to grow uncontrollably metastasize Regulating Agents of the Cell Cycle Regulating agents are Proteins whose concentrations rise & fall in a controlled manner If agent concentration is high, cycle progresses; if it is low, cycle is suspended Cell cycle control focused 2 places 62 Cell cycle control is focused at 2 places: Control of the Cell Cycle Before S phase (DNA synthesis) At transition between G 2 and M phase Control of Regulating Agents Regulating agents can be controlled by proximity of other cells Regulating agents can be controlled by factors inside the cell itself Internal & external stimuli activate or inhibit regulating agents These, in turn activate enzymes to help cells divide Control of the Cell Cycle Internal checkpoints & guardians monitor cell health Errors in this process can lead to uncontrollable growth and cancer 65