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Organization of DNA DNA ð RNA ð PROTEIN Housekeeping information Tom Hartman Figure 3–11 DNA as chemistry Organization of DNA Figure 3–11 DNA as data storage DNA as a molecular model Note: A-T C-G A – adenine T – thymine C – cytosine G – guanine 1 PDF created with pdfFactory Pro trial version www.software-partners.co.uk DNA as heredity Organization of DNA • Double helix – and associated proteins • Nucleosomes: – DNA coiled around histones • Chromatin: – loosely coiled DNA (cells not dividing) • Chromosomes: – tightly coiled DNA (cells dividing) DNA and Genes • DNA: – instructions for every protein in the body What is genetic code? • Gene: – DNA instructions for 1 protein – DNA instructions for RNA (new) Genetic Code • The chemical language of DNA instructions: – sequence of bases (A, T, C, G) – triplet code: • 3 bases = 1 amino acid A – adenine T – thymine C – cytosine G – guanine KEY CONCEPT • • • • The nucleus contains chromosomes Chromosomes contain DNA DNA stores genetic instructions for proteins Proteins determine cell structure and function 2 PDF created with pdfFactory Pro trial version www.software-partners.co.uk Protein Synthesis • Transcription: How do DNA instructions become proteins? Protein Synthesis • Processing: – copies instructions from DNA to mRNA (in nucleus) • Translation: – ribosome reads code from mRNA (in cytoplasm) – assembles amino acids into polypeptide chain mRNA Transcription • A gene is transcribed to mRNA in 3 steps: – by RER and Golgi apparatus produces protein – gene activation – DNA to mRNA – RNA processing • Physical chemical configurations code for data: start ð copy ð stop DNA polarity • DNA is a double stranded molecule. • Each strand is a polynucleotide and, at the chemical level, the strands start with a free 5’-hydroxyl group and end with a 3’-hydroxyl. • The strands run antiparallel 5’-3’ vs 3’-5’ with the appropriate nucleotides pairing A-T, C-G. • The two stranded, antiparallel, complementary DNA molecule forms the double helix. • One strand, the sense or coding strand, contains the information (the genes). • The other strand is the template or antisense strand. Codons • A codon is a three letter ‘word’. • The start is defined by an initiation ‘word’. • Each three letter ‘word’ is a reading frame and if the frame shifts by one letter then the result could be very different and may be lethal! • RNA uses uracil not thymine 3 PDF created with pdfFactory Pro trial version www.software-partners.co.uk Codons • 5’-3’ ATCGTACCG • 3’-5’ TAGCATGGC • 5’-3’ AUCGUACCG Step 1: Gene Activation sense strand antisense strand mRNA • Uncoils DNA, removes histones • Start (promoter) and stop codes on DNA mark location of gene: – coding strand is code for protein – template strand used by RNA polymerase molecule Step 2: DNA to mRNA Step 3: RNA Processing • Enzyme RNA polymerase transcribes DNA: • At stop signal, mRNA detaches from DNA molecule: – binds to promoter (start) sequence – reads DNA code for gene – binds nucleotides to form messenger RNA (mRNA) – mRNA duplicates DNA coding strand, uracil replaces thymine – – – – code is edited (RNA processing) unnecessary codes (introns) removed good codes (exons) spliced together triplet of 3 nucleotides (codon) represents one amino acid Codons Anatomy of a gene Stop Start Intron • • • • • Genes are located on the sense strand mRNA is coded off the antisense strand Gene has a start codon whichis often ATG (methionine elsewhere). Eukarytoic genes have introns (edited off the mRNA in the nucleus and spliced) Genes have stop signals (termination) – UAG (amber) – UGA (opal/umber) – UAA (ochre) Table 3–2 4 PDF created with pdfFactory Pro trial version www.software-partners.co.uk An amino acid wheel Degeneracy of the genetic code • There are 20 aas and a stop code. • There are 4 bases and a need for 21 codes. • Two letter codes would give 42=16 codes whereas 43=64 codes. • Thus there may be several ways to code for an amino acid. (e.g. valine could be GUA, GUU, GUC, GUG) • This may protect against point mutations. Sickle cell anaemia Translation (1 of 6) • One amino acid difference • mRNA moves: – Valine replaces Glutamic acid – from the nucleus – through a nuclear pore • One nucleotide change – GTA replaces GAA (GUA replaces GAA in mRNA) • Huge change in protein morphology at low [O2] as haemoglobin crystallizes causing RBC to change shape. • But it does give some measure of protection against malaria. Figure 3–13 Translation (2 of 6) Translation (3 of 6) • mRNA moves: – to a ribosome in cytoplasm – surrounded by amino acids • mRNA binds to ribosomal subunits • tRNA delivers amino acids to mRNA Figure 3–13 (Step 1) Figure 3–13 (Step 2) 5 PDF created with pdfFactory Pro trial version www.software-partners.co.uk Translation (4 of 6) Translation (5 of 6) • tRNA anticodon binds to mRNA codon • 1 mRNA codon translates to 1 amino acid • Enzymes join amino acids with peptide bonds • Polypeptide chain has specific sequence of amino acids Figure 3–13 (Step 3) Translation (6 of 6) Figure 3–13 (Step 4) Note the preponderance of RNA • rRNA in the production and activity of ribosomes. • mRNA transcribing (editing and splicing) genes. • tRNA transporting and assembling polypeptides. • This has been taken as a hint of the primacy of RNA in the history of life. • At stop codon, components separate Figure 3–13 (Step 5) Nucleus Controls Cell Structure and Function • Direct control through synthesis of: – structural proteins – secretions (environmental response) • Indirect control over metabolism through enzymes KEY CONCEPT • Genes: – are functional units of DNA – contain instructions for 1 or more proteins – Occasionally just RNA • Protein synthesis requires: – several enzymes – ribosomes – 3 types of RNA 6 PDF created with pdfFactory Pro trial version www.software-partners.co.uk KEY CONCEPT • Mutation is a change in the nucleotide sequence of a gene: – can change gene function • Causes: – exposure to chemicals – exposure to radiation – mistakes during DNA replication 7 PDF created with pdfFactory Pro trial version www.software-partners.co.uk