Lecturer: 譚賢明 助理教授Office: 醫學大樓十樓生科系 B 區Phone: 5067Textbook: Stryer’s Biochemistry (6th 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:Genetic information:

1. Duplication: DNA replication

2. Decoding:

DNA RNA proteintranscriptionRNA processing

translation

Nucleoside: base bonded to a sugar(deoxy)adenosine, (deoxy)quanosine, (deoxy)cytidine, (deoxy)uridinethymidine

N-9 (purine) orN-1 (pyrimidine)

C-1’ sugar

Nucleotide: nucleoside joined to one or more phosphateNucleoside 5’-phosphate, or 5’-nucleotide

C-5’ sugarester 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 bonddonors and acceptors

Negative charge

DNA: double helix of complementary antiparallel strands

Hydrophobicvan der Waals

Hydrogen bonding(Watson-Crick base pairs)

Hydrophobicvan der Waals

Axial view of DNA: stacked bases

DNA can undergo reversible strand separation

“Denaturation” or “meting” : DNA unwinding1. In vivo: DNA replication and transcription2. In vitro: thermal energy

Factors influencing melting temperature (Tm)1. Base content (G-C vs. A-T)2. Ion concentration3. Agents that destabilize H-bonds

(ex. formamide or urea)4. pH

Denatured random coilsRenatured double stranded by complementarity

(ex. nucleic acid hybridization)

Some DNA molecules are circular and supercoiled

1. Human chromosomes are linear2. DNA molecules from other organisms are “circular”3. Inside cells, DNA has very compact shape4. Superhelix: double helix can itself be twisted or

supercoiled5. “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. Polynucleotide2. 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 acids2. Double-strand DNA3. Strands annealing vs. separation4. Secondary and tertiary structures:

*supercoils*RNA