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The Central Dogma Of Molecular Biology. DNA replication. DNA. transcription. Chromosome synthesis: 2 chromatids NOT NEEDED IN GENE EXPRESSION!. RNA. Polypeptide. translation. Normal Gene Function. DNA. transcription. RNA. Polypeptide. translation.
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The Central Dogma Of Molecular Biology DNA replication DNA transcription Chromosome synthesis: 2 chromatids NOT NEEDED IN GENE EXPRESSION! RNA Polypeptide translation
Normal Gene Function DNA transcription RNA Polypeptide translation
Relationship Between Genes and Proteins • Archibald Garrod • Early 1900’s • Worked with “inborn errors of metabolism” • diseases caused by lack of an enzyme • alkaptonuria • arthritis • darkening of urine • First stated enzymes were inherited
Relationship Between Genes and Proteins • Beadle and Tatum • 1940’s • Worked with neurospora • produced mutations in different genes • each mutation caused loss of function of an enzyme • “One gene - one enzyme” paradigm
Relationship Between Genes and Proteins One gene - one enzyme paradigm has been refined: One gene - one polypeptide
Molecular Basis of Sickle Cell Anemia • Illustrates one gene - one polypeptide • Problem with hemoglobin • hemoglobin is made of four polypeptides • two alpha polypeptides + two betas • Sickle cell hemoglobin differs from normal hemoglobin in only the beta polypeptide; alphas are identical
Normal b - chain 146 amino acids Sickle cell b - chain 146 amino acids Molecular Basis of Sickle Cell Anemia val his leu thr pro GLU glu 1 1 val his leu thr pro VAL glu 146 146
Molecular Basis of Sickle Cell Anemia Difference of only one out of 146 amino acids! DNA codes: Glutamic acid Valine G A A G T A G A G GT G
DNA, Polypeptides, and Proteins • Sequence of bases in DNA codes for a sequence of amino acids • chains of amino acids are polypeptides • polypeptides may be proteins • proteins may have a variety of functions, including being enzymes
Amino Acids R HN C C OH H H O amino group carboxylic acid group
Polypeptide vs. Protein • Chain of amino acids = polypeptide • functional polypeptide = protein • if single polypeptide is not functional = protein “Protein” is a functional term enzymes are special types of proteins
Levels of Protein Structure • 1o - sequence of amino acids • 2o - hydrogen bonding between NH2 of one a.a. and COOH of another • a - helix • b - pleated sheet • random coil • 3o - interactions between R groups • 4o - 2 or more polypeptides
RNA A U G C G A A A A U G C A T G C G A A A A T G C T A C G C T T T T A C G DNA transcription translation MET - ARG - LYS - CYS polypeptide Sequences of bases turned into sequences of amino acids!