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

Nucleic acid metabolism: Overview Ch. 28 Ch. 29,31 Ch. 30 Ch. 4,5

Nucleic acid metabolism: Overview Genetic information: 1.Duplication:  DNA replication 2.Decoding: DNA  RNA  protein transcription RNA processing translation

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

Nucleotide: nucleoside joined to one or more phosphate Nucleoside 5’-phosphate, or 5’-nucleotide C-5’ sugar ester linkage Adenosine 5’-triphosphate

Sugars in nucleic acids are linked by phosphodiester bonds (also called the backbone)

Negative charge of the backbone repels nucleophilic species  Important for maintaining structure and information Which is more stable?

DNA & RNA: linear polymer with directionality (polynucleotide chain) bases have hydrogen bond donors and acceptors Negative charge

DNA: double helix of complementary antiparallel strands Hydrophobic van der Waals Hydrogen bonding (Watson-Crick base pairs)

Hydrophobic van der Waals

Axial view of DNA: stacked bases

DNA can undergo reversible strand separation “Denaturation” or “meting” : DNA unwinding 1.In vivo: DNA replication and transcription 2.In vitro: thermal energy

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)

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

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)

RNA secondary and tertiary structures

tRNA and rRNA have tertiary structures (some mRNA too, at 3’ ends)

Summary: Molecules of Heredity 1.Nucleic acids 2.Double-strand DNA 3.Strands annealing vs. separation 4.Secondary and tertiary structures: *supercoils *RNA