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The Nucleic Acids

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The Nucleic Acids

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Collin mirisi
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© © All Rights Reserved
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THE NUCLEIC ACIDS

Friedrich Miescher in 1869


• isolated what he called nuclein from the
nuclei of pus cells
• Nuclein was shown to have acidic properties,
hence it became called nucleic acid

© 2007 Paul Billiet ODWS


Two types of nucleic acid are found
• Deoxyribonucleic acid (DNA)
• Ribonucleic acid (RNA)

© 2007 Paul Billiet ODWS


The distribution of nucleic acids in the
eukaryotic cell
• DNA is found in the nucleus
with small amounts in mitochondria and
chloroplasts
• RNA is found throughout the cell

© 2007 Paul Billiet ODWS


DNA as genetic material: The
circumstantial evidence
1. Present in all cells and virtually restricted to the nucleus
2. The amount of DNA in somatic cells (body cells) of any given
species is constant (like the number of chromosomes)
3. The DNA content of gametes (sex cells) is half that of somatic
cells.
In cases of polyploidy (multiple sets of chromosomes) the DNA
content increases by a proportional factor

© 2007 Paul Billiet ODWS


NUCLEIC ACID STRUCTURE
• Nucleic acids are polynucleotides
• Their building blocks are nucleotides

© 2007 Paul Billiet ODWS


NUCLEOTIDE STRUCTURE

PHOSPATE SUGAR BASE


PURINES PYRIMIDINES
Ribose or
Deoxyribose Adenine (A) Cytocine (C)
Guanine(G) Thymine (T)
Uracil (U)

NUCLEOTIDE
© 2007 Paul Billiet ODWS
Ribose is a pentose

C5

C4 C1

C3 C2

© 2007 Paul Billiet ODWS


Spot the difference

RIBOSE DEOXYRIBOSE

CH2OH CH2OH
O OH O OH

C C C C

H H H H H H H H

C C C C

OH OH OH H
© 2007 Paul Billiet ODWS
Sugars

HOCH2 O OH HOCH2 O OH

OH OH OH (no O)

ribose deoxyribose

11
P

THE SUGAR-PHOSPHATE
BACKBONE P

• The nucleotides are all


orientated in the same P

direction
• The phosphate group joins the P

3rd Carbon of one sugar to the


5th Carbon of the next in line. P

© 2007 Paul Billiet ODWS


P
G

ADDING IN THE BASES P


C

• The bases are


attached to the 1st P
C
Carbon
• Their order is P
important A

It determines the
genetic information P
T
of the molecule
P
© 2007 Paul Billiet ODWS
T
Hydrogen bonds
P

DNA IS MADE OF G C
P
TWO STRANDS OF P
POLYNUCLEOTIDE C G
P
P
C G
P
P
A T
P
P
T A
P
P
T A
© 2007 Paul Billiet ODWS
P
DNA IS MADE OF TWO STRANDS OF
POLYNUCLEOTIDE
• The sister strands of the DNA molecule run in opposite
directions (antiparallel)
• They are joined by the bases
• Each base is paired with a specific partner:
A is always paired with T
G is always paired with C
Purine with Pyrimidine
• This the sister strands are complementary but not
identical
• The bases are joined by hydrogen bonds, individually
weak but collectively strong

© 2007 Paul Billiet ODWS


Structure of Nucleic Acids

• Polymers of four nucleotides


• Linked by alternating sugar-phosphate bonds
• RNA: ribose and A, G, C, U
• DNA: deoxyribose and A,G,C,T

base base base base

P sugar P sugar P sugar P sugar


nucleotide nucleotide nucleotide nucleotide
16
Nucleic Acid Structure
NH2

N
CMP
O O N
O- P O CH2
-
O
O
3
3,5-phosphodiester bond NH2
OH N
N

5O N N
O P O CH2
-
O AM P
O

17 OH
Double Helix of DNA

• DNA contains two strands of nucleotides


• H bonds hold the two strands in a double-helix
structure
• A helix structure is like a spiral stair case
• Bases are always paired as A–T and G-C
• Thus the bases along one strand complement the
bases along the other

18
Double Helix of DNA

19
Learning Check NA1

Write the complementary base sequence for the


matching strand in the following DNA section:

-A-G-T-C-C-A-A-T-G-C-
• • • • • • • • • •
• • • • • • • • • •

20
Solution NA1

Write the complementary base sequence for the


matching strand in the following DNA section:

-A-G-T-C-C-A-A-T-G-C-
• • • • • • • • • •
• • • • • • • • • •
-T-C-A-G-G-T-T-A-C-G-

21
DNA Replication

• DNA in the chromosomes replicates itself every cell


division
• Maintains correct genetic information
• Two strands of DNA unwind
• Each strand acts like a template
• New bases pair with their complementary base
• Two double helixes form that are copies of original
DNA

22
DNA

23
Unwinding of DNA by helicases expose the DNA bases
(replication fork) so that replication can take place. Helicase
hydrolyzes ATP in order to break the hydrogen bonds between
DNA strands

DNA replication

24
DNA Unwinds

G- -C
G-C A- -T
A-T C- -G
C-G T- -A
T-A

25
DNA Copied with Base Pairs

Two copies of original DNA strand

G-C G-C
A-T A-T
C-G C-G
T-A G-A

26
Replication of DNA.

DNA DNA transcription mRNA translation Protein


replication
(genome) (transcriptome) (proteome)

Expression and transfer of genetic information:


Replication: process by which DNA is copied with very high
fidelity.
Transcription: process by which the DNA genetic code is read
and transferred to messenger RNA (mRNA). This is an
intermediate step in protein expression
Translation: The process by which the genetic code is converted
to a protein, the end product of gene expression.
The DNA sequence codes for the mRNA sequence, which
27
codes for the protein sequence
For replication, DNA must be unknotted, uncoiled and the double
helix unwound.
Topoisomerase: Enzyme that unknots and uncoils DNA
Helicase: Protein that unwinds the DNA double helix.
DNA polymerase: Enzyme that DNA is replicated by the coordinated
efforts of a number of
replicates proteins and enzymes.
DNA using each strand
as a template for the newly synthesized strand.
DNA ligase: enzyme that catalyzes the formation of the
phosphodiester bond between pieces of DNA.

DNA replication is semi-conservative: Each new strand of DNA


contains one parental (old, template) strand and one
28 daughter (newly synthesized) strand
DNA Polymerase: the new strand is replicated from the 5’  3’
(start from the 3’-end of the template)
DNA polymerases are Mg2+ ion dependent
The deoxynucleotide 5’-triphosphate (dNTP) is the reagent for
nucleotide incorporation
OH dNTP
5'
O O O
O O P O P O P O-
A T O- O- O-
O O OH Mg2+

O O O
O P G C
-O O O
(new)
5'
template
strand O
(old)
3'

3’-hydroxyl group of the growing DNA strand acts as a nucleophile


and attacks the -phosphorus atom of the dNTP.
29
Replication of the leading strand occurs continuously in the
5’  3’ direction of the new strand.
Replication of the lagging strand occurs discontinuously. Short
DNA fragments are initially synthesized and then ligated together.
DNA ligase catalyzes the formation of the phosphodiester bond
between pieces of DNA.

30
animations of DNA processing: http://www.wehi.edu.au/education/wehi-tv/dna/
DNA replication occurs with very high fidelity:
Most DNA polymerases have high intrinsic fidelity
Many DNA polymerases have “proof-reading”
(exonuclease) activity
Mismatch repair proteins seek out and repair base-pair
mismatches due to unfaithful replication
28.11 Ribonucleic Acid
RNA contains ribose rather than 2-deoxyribose and uracil rather
than thymine. RNA usually exist as a single strand.

There are three major kinds of RNA


messenger RNA (mRNA):
ribosomal RNA (rRNA)
transfer RNA (tRNA)

DNA is found in the cell nucleus and mitochondria; RNA is more


disperse
31
in the cell.
Transcription: only one of the DNA strands is copied
(coding or antisense strand).

An RNA polymerase replicates the DNA sequence into a


complementary sequence of mRNA (template or sense
strand).
mRNAs are transported from the nucleus to the cytoplasm,
where they acts as the template for protein biosynthesis
(translation). A three base segment of mRNA
(codon) codes for an amino acid.

32
5'-cap 5'-UTR start Coding sequence stop 3'-UTR

The mRNA is positioned in the ribosome through complementary


pairing of the 5’-untranslated region of mRNA with a rRNA.
Transfer RNA (tRNA): t-RNAs carries an amino acid on the
3’-terminal hydroxyl (A) (aminoacyl t-RNA) and the ribosome
catalyzes amide bond formation.

Ribosome: large assembly of proteins and rRNAs that catalyzes


protein and peptide biosynthesis using specific, complementary,
anti-parallel pairing interactions between mRNA and the
anti-codon loop of specific tRNA’s.

33
Although single-stranded, there are complementary sequences
within tRNA that give it a defined conformation.
The three base codon sequence of mRNA are complementary
to the “anti-codon” loops of the appropriate tRNA. The base-
pairing between the mRNA and the tRNA positions the tRNAs
for amino acid transfer to the growing peptide chain.

variable loop

TC loop

D loop

aminoacyl t-RNA
34

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