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The Charles B. Huggins Lectures, 2006 'Breast Cancer: the Genetics of a Disease' James D. Fackenthal, Ph.D. University of Chicago

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The Charles B. Huggins Lectures, 2006 Saturdays from 11:00 AM – 12:00 PM Jan 14. Overview and introduction to cancer Jan 21. Early experiments in genetics: the science of heredity Jan 28. Later experiments in genetics: the science of molecular biology Feb 4. The DNA double helix: structural basis of heredity and molecular biology Feb 11. Gene mutations and cancer, part 1: oncogenes and tumor suppressor genes regulate tumor development Feb 18. Gene mutations and cancer, part 2: hormone action in normal cells and breast tumors Feb 25. Genetic studies point the way to better treatments March 4. From Genetics to Genomics.

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How does DNA carry genetic information? Biochemistry, 5th ed. Berg, Tymoczko, Stryer. W.H. Freeman and Company, 2002, New York Chemical components of DNA: bases

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How does DNA carry genetic information? Biochemistry, 5th ed. Berg, Tymoczko, Stryer. W.H. Freeman and Company, 2002, New York Bases are attached to sugars (ribose or deoxyribose) and phosphate groups to form nucleotides. Deoxycytodine 5’ triphosphate (dCTP)

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X-ray crystallography General Chemistry, 2nd ed. Ebbing and Wrighton. Houghton Mifflin Co. 1987 Boston

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X-ray diffraction patterns from DNA The Eighth Day of Creation. Judson. Simon and Schuster, 1979, New York

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DNA is a helical molecule composed of two strands Minor groove Major groove Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, New York, 2002

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Edwin Chargaff’s Rules 1. In DNA, the total amount of pyrimidine nucleotides (T and C) always equals the total amount of purine nucleotides (A and G). 2. The amount of T always equals the amount of A, and the amount of C always equals the amount of G.

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What do Chargaff’s rules mean? Biochemistry, 5th ed. Berg, Tymoczko, Stryer. W.H. Freeman and Company, 2002, New York The bases in DNA bind to each other by hydrogen bonding. This is the basis of base pairing.

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What do Chargaff’s rules mean? Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York Pu = Py A = T G = C

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Base pairing on the inside, backbone on the outside Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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DNA is copied (or replicated) by addition of nucleotides to a new strand using the old strand as a template Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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DNA polymerase adds bases to the end of a new strand of DNA Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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DNA replication is semi-conservative Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York Each newly replicated DNA molecule contains one new strand and one old strand.

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DNA replication starts at specific places on the chromosome, generating replication forks Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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RNA is like DNA, with some exceptions Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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RNA is transcribed from DNA in a way similar to DNA replication Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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Transcription generates RNA molecules copied from one DNA strand Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York RNA transcription starts at specific places on the chromosome and proceeds to specific stopping places

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Amino acids are the building blocks of proteins Biochemistry, 5th ed. Berg, Tymoczko, Stryer. W.H. Freeman and Company, 2002, New York

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Amino acids are linked by peptide bonds into long chains (polypeptides) Biochemistry, 5th ed. Berg, Tymoczko, Stryer. W.H. Freeman and Company, 2002, New York

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Polypeptides fold into functional shapes (proteins). Some proteins are enzymes. Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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The order of amino acids in a polypeptide is determined by a triplet base code in RNA -UUUUUUUUUUUUUUUUUU- Phe Phe Phe Phe Phe Phe

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The triplet base code is redundant An Introduction to Genetic Analysis, Griffiths et al. W.H. Freeman and Company, 2000, New York

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Transfer RNA (tRNA) molecules are charged with amino acids Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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The ribosome uses tRNAs to add amino acids to growing polypeptides using mRNA as a template Molecular Biology of the Cell, 4th ed. Alberts et al. Garland Science Textbooks, 2002, New York

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Major points: the structure of DNA explains both Mendelian inheritance and one gene-one enzyme

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