Mahasiswa Baru Fakultas Kedokteran Universitas Airlangga Tahun 2007 - 2008

Dra Sri Mustaina, MKes. September 2007

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Structure of The Nucleic Acid

Molecule size > protein Synthesized at : cell nuclei; mitochondria; plastid Nucleic Acid is polymers of Nucleotides : DNA & RNA Each nucleotide consist of : 1. Pentose sugar Ribose sugar Deoxyribose sugar 2. Nitrogenous base Purine Pyrimidine 3. Phosphate. Function : as genetic material

RNA DNA

Organization of Human DNA

Size of DNA molecules : haploid cells : 3,0 x 109 base pairs 1 chromosome 7 cm in length total length ( 46 chromosomes) 1,7 m. Packing of DNA in cells : Double helix wound around (histone) proteins that organize & protect DNA. DNA-protein packages coiled in larger coils. More twisting & condensation chromosome. Function : Genetic Material 1. Able to replicate 2. Able to encode the sequence of protein 3. Able to change in a controlled way

Packing of DNA in cells

- DNA interacts with basic proteins known as histones - Histones arginine and lysine - Five classes of histones : H1, H2A, H2B, H3 and H4 H2A H2B Ellipsoid H3 H4 - Other types of proteins are also associated with DNA - Nucleosomes : * bead-like structures of DNA * DNA coils around the surface of the ellipsoid * Complex of histones plus DNA

Deoxyribonucleic Acid ( DNA )

Nucleotide Structure : Deoxyribose Sugar Nitrogenous Base : Purine : - Adenine & Guanine

Pyrimidine : - Cytosine & Thymine Phosphate

Nucleotides of DNA

Bases Pairing
By Hidrogen Bond

Purines - Pyrimidines

Adenine Thymine Guanine Cytosine

Characteristic of DNA
- Denature : The two strands of the DNA helix separate or denature * Alkali * Heat

OH-_

OH-_

DNA

DNA

RNA

DNA

RNA

Effect of alkali on DNA and RNA. : DNA strands stay intact, but separate. RNA strands are degraded to nucleotides.

Characteristic of DNA
- Renaturation (reannealing) : temperature slowly re-forming a double helix, identical to the original DNA.

Heat Cool

ary m Pri eric lym ure Po ct tru f S o A DN

The Secondary Structure of DNA

THE DOUBLE HELIX 1. Two antiparallel strands form a right-handed helix 2. Complementary base pairing

Various diagrammatic ways of representing DNA : (a) showing polarity and base pairing but no helical twist; (b) showing helical twist and helix parameters but not base pairs;

(a )

(b)

Various diagrammatic ways of representing DNA : (c) showing helix and base pairs; (d) space-filling representation showing major and minor grooves.

Twist

A double helix

Z, B, and A forms of DNA. The solid black lines connect one phosphate group to the next.

Two DNA strand twisted to form a double helix

DNA helix

DNA Replication
prepared genetic material to reproduction / cell division

Replication rate - The eukaryotic replication rate is about 10 times slower than the prokaryotic replication rate. - 8 hours to replicate the human genome semi conservative mechanism bidirectional, direction of DNA synthesize : 5 3 start at many Origin of Replication (ORI)

Semi conservative

Synthesis always goes from 5 to 3

Schematic representation of the addition of a nucleotide to a growing strand of DNA during replication.

Phosphate O CH2 O 4 H H H 3 OH H

Base

1 H 2 H

Next nucleotide will joined here

Bi-directional

4 Stages in Replication Process

1. Unwind the helix : - Topoisomerase - With the aid of DNA gyrase - Helicase - SSBP 2. DNA is replicated by DNA Polymerase - Primase - DNA Polymerase III - Leading and Lagging Strand - Okazaki Fragment 3. Removal the RNA primer - DNA Polymerase I 4. Joint the fragment - DNA lygase

Emzymes required on DNA replication

1. Topoisomerase : initiation of unwinding of DNA 2 Helicase : accomplishes unwinding original double strand DNA 3. Single-stranded binding protein : stabilized single strand DNA as templates to RNA primase and DNA pol. 4. Primase : to attaches a small RNA primer 5.DNA Polymerase : proceed along single-stranded molecule of DNA 6. Ligase : organize and catalyze formation phosphodiester bond on the 3 end.

Structure of RNA
Single stranded RNA nucleotides consist of: 1. Ribose (a pentose = sugar with 5 carbons) 2. Phosphate group 3. Organic (nitrogenous) bases: - Pyrimidines (Cytosine and Uracil) - Purines (Adenine and Guanine)

RNA - Function
- Information storage and transport (mRNA, viral RNA) - Info transfer - Catalysis -ribozymes - Ribosome Regulation - Plasmid copy # (tRNA)

RNA Codons
Start codon : Stop codon : AUG UAA, UAG and UGA

4 kinds of RNA, made by cell

mRNA = messenger RNA is a copy of a gene, carry the information stored DNA nucleus to cytoplasm (translation machine) tRNA = transfer RNA as an adaptor to carry aa to appropriate place as coded by mRNA rRNA = ribosomal RNA structural component of ribosomes snRNA= small nuclear RNA involve in the machinery that process RNAs between nucleus and cytoplasm in

Difference between RNA

DNA-

DNA repair

Mismatch repair

Base excision repair

Nucleotide excision repair

Double-strand break repair