Fig. 9-CO,

Nucleic acid: how structure conveys information

Genetic materialGene-chromosome

親子鑑定 ???

DNA-RNA- Protein

deoxyribonucleic acidribonucleic acid

Nucleic Acids

• Nucleic acid:Nucleic acid: a biopolymer containing three types of monomer units

– a base derived from purine or pyrimidine (nucleobases) – a monosaccharide, either D-ribose or 2-deoxy-D-ribose

(nucleoside)– phosphoric acid

• RNA (Ribonucleic Acid)

• DNA (Deoxyribonucleic Acid)

Nucleotide (核甘酸 )

Fig. 9-1

Common nucleobases: primary structure

Fig. 9-2,

Less common nucleobases

Fig. 9-3,

Ribonucleoside & deoxyribonucleoside: -D-ribose and nucleobase

N-glycosidic linkage

N1-pyrimidineN9-purine

Fig. 9-4,

Adding phosphoric acid-nucleotide

AMP, ADP, ATP

Esterified

Fig. 9-4a (1), p. 238

Fig. 9-5,

Polymerization3’,5’-phosphodiester bondSugar-phosphate backbone

pApCpGpU

Fig. 9-6,

pd(TGCA)

The DNA family tree

fossil Ancient DNA amber

(polynucleotides)

Nucleic Acids

• Levels of structure– 1°structure: the order of bases on the

polynucleotide sequence; the order of bases specifies the genetic code

– 2°structure: the three-dimensional conformation of the polynucleotide backbone

– 3°structure: supercoiling– 4°structure: interaction between DNA and

proteins

Fig. 9-7,

Double helix-1953-Watson & Crick-X ray

One turn—3.4 nm 10 base pairs

Negative chargeMajor & minor groove

AntiparallelComplementary strandA=T, G=C

secondary structure

Fig. 9-8

1

6

12

Fig. 9-9a,

B-DNA-major: 10 bp-right-handed

Z-DNA-GC rich left –handed

A-DNA-11bp, not in vivo (dehydrated DNA), right handed

Fig. 9-10,

Fig. 9-11,

GC rich

Zigzag: 180O

Fig. 9-12,

Best pairing(but not stacking)

Helical twist

Expose to water at minor groove

Fig. 9-13,

Stacking-propeller-twisted base pairs

Eliminate water contact

Ring portion is hydrophobicStacking better than pairing

Fig. 9-15,

Supercoiled DNA-tertiary structure

Fig. 9-16

Topoisomerase-type1: one strand type2: double strand

DNA gyrase

Fig. 9-17

Chromatin-DNA+ Protein (histone)Histone-positive charge H1, H2A, H2B, H3, H4

Nucleosome150 base pairs and(H2A)2(H2B)2(H3)2(H4)2

Spacer region: 30-50 base pairs andhistone 1 & others

The structure of chromatin

Insertiondeletion

Insertion and deletion

Mutation rate around nucleosome

Nucleotide changes

Methylation and Acetylation of histones regulates expression of genes

Gene off

Gene on

Disease and epigenetic statesCancer immune deficiencies Diabetes heart disease

DNA methylation: shutting off

Why identical twins are not identical

Microarrays coded to show epigenetic differences

DNA sequence is the same

Gene expressionDNA methylation—5-methylcytosineTurn off expression (in Z DNA)

Fig. 9-18

DNA denaturation

H bond, stacking

Melting

hyperchromicity

OD260 nm

Fig. 9-19

DNA denaturationPCR reaction (amplification of DNA)

Fig. 9-20

Information transfer in cells

Replication

Transcription

Translation

Fig. 9-21

The role of mRNA in transcription

snRNPs: snRNA + proteins

mRNA:Small amount and Very short-lived

100-200 nts

Table 9-1

Fig. 9-22

Transfer RNA-cloverleaf

1 amino acid :1 tRNA or more

80 nts

Stem and loop

Fig. 9-23

Modified bases in transfer RNA

Fig. 9-24

Three dimensional structure of tRNA

3 nucleotides: 1 amino acid

Fig. 9-26

E. Coli 70S

Reduce Mg 2+ dissociationreversible

The structure of typical ribosome

antibiotics

Fig. 9-25

The analytical ultracentrifuge

Sedimentation coefficient

Svedberg unit (S)

Molecular weight and shape

Fig. 9-27

Secondary structure for 16S ribosomal RNA

1500 nts500 KDa

Micro RNA :Regulation of geneExpression

dsRNA (siRNA):Used by scientiststo knock down a gene

Adopted from giuworld.com

The human Genome project

3.3 billion base pair30,000 genes (25,000)

EthicalLegalSocial implications

Gene therapy

Genome on a ID card

Synthetic genome created (2009) Watermark—blue colonies