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Lecturer: 譚賢明 助理教授 Office: 醫學大樓十樓生科系 B 區 Phone: 5067 Textbook: Stryer’s Biochemistry (6 th ed.) (Chapters 4, 5, 28-31) Lewin’s Cells (Chapters 5 & 6) 分子細胞生物學 Part I
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Nucleic acid metabolism: Overview Ch. 28 Ch. 29,31 Ch. 30 Ch. 4,5
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Nucleic acid metabolism: Overview Genetic information: 1.Duplication: DNA replication 2.Decoding: DNA RNA protein transcription RNA processing translation
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Nucleoside: base bonded to a sugar (deoxy)adenosine, (deoxy)quanosine, (deoxy)cytidine, (deoxy)uridine thymidine N-9 (purine) or N-1 (pyrimidine) C-1’ sugar
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Nucleotide: nucleoside joined to one or more phosphate Nucleoside 5’-phosphate, or 5’-nucleotide C-5’ sugar ester linkage Adenosine 5’-triphosphate
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Sugars in nucleic acids are linked by phosphodiester bonds (also called the backbone)
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Negative charge of the backbone repels nucleophilic species Important for maintaining structure and information Which is more stable?
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DNA & RNA: linear polymer with directionality (polynucleotide chain) bases have hydrogen bond donors and acceptors Negative charge
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DNA: double helix of complementary antiparallel strands Hydrophobic van der Waals Hydrogen bonding (Watson-Crick base pairs)
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Hydrophobic van der Waals
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Axial view of DNA: stacked bases
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DNA can undergo reversible strand separation “Denaturation” or “meting” : DNA unwinding 1.In vivo: DNA replication and transcription 2.In vitro: thermal energy
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Factors influencing melting temperature (Tm) 1.Base content (G-C vs. A-T) 2.Ion concentration 3.Agents that destabilize H-bonds (ex. formamide or urea) 4.pH Denatured random coils Renatured double stranded by complementarity (ex. nucleic acid hybridization)
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Some DNA molecules are circular and supercoiled 1.Human chromosomes are linear 2.DNA molecules from other organisms are “circular” 3.Inside cells, DNA has very compact shape 4.Superhelix: double helix can itself be twisted or supercoiled 5.“Supercoiling” is biological important because: * supercoiled DNA is more compact than “relaxed” * supercoiling affect the capacity of double helix to unwind --> interaction between DNA and other molecules
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DNA vs. RNA Difference: 1.Hydroxyl group at 2’ position (RNA is unstable in alkaline solution) 2.Uracil instead of thymine Similarity: 1.Polynucleotide 2.Double-stranded (ds), single stranded (ss), linear, circular (RNA is linear ss in vivo)
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RNA secondary and tertiary structures
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tRNA and rRNA have tertiary structures (some mRNA too, at 3’ ends)
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Summary: Molecules of Heredity 1.Nucleic acids 2.Double-strand DNA 3.Strands annealing vs. separation 4.Secondary and tertiary structures: *supercoils *RNA
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