Download Nucleic acids

Nucleic acids: DNA and RNA
Done By
Majed Felemban
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DNA
• Double helix
– 2 chains
• Building blocks
– Nucleotides
• DNA directs
– Is own replication
– Directs RNA synthesis → protein synthesis
Campbell and Reece, P86
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In Eukaryotes (animals, plants, fungi)
Complete human genome
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In Prokaryotes (bacteria, archaea)
• Main chromosome is
one large, continuous
loop
– Hundreds to thousands
of genes
• May have smaller
loops, with a few genes
each
– May be swapped
between bacteria
– Antibiotic resistance, etc.
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Replication
Transcription
Translation
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Roles of Nucleic Acids
• DNA
– Responsible for inheritance
– Codes for proteins and functional RNAs
• Genes
– Regulatory sequences
• Control which genes are transcribed, and when
– Other unknown functions
• 80-90% of the human genome has no known function
Campbell and Reece, P86, 87
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Roles of Nucleic Acids
• RNA
–
–
–
–
–
–
Information transmission (mRNA)
Processing and transport (tRNA, rRNA, snRNA)
Catalytic (ribozymes)
Regulation and feedback (siRNA)
Unit of inheritance (retroviruses)
Other…?
Campbell and Reece, P86, 87
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NUCLEIC ACID STRUCTURES
• Nucleic Acid chemistry is the same for all life on earth.
• DNA & RNA are polymers of monomers - nucleotides.
• Each nucleotide has three components
N
O
O
NH2
-
O
O
X
OH
P
O
OH
N
N
N
OH
N
O
-
O
(Deoxy)ribonucleic Acid
O
-
O
OH
X
OH
P
O
1.
PHOSPHORIC ACID = STRUCTURAL
2.
(DEOXY)RIBOSE SUGAR = STRUCTURAL
3.
NITROGENOUS BASES = INFORMATIONAL
Campbell and Reece, 86
O
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Campbell and Reece, P87
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Phosphoric Acid & Related Compounds
D
• Phosphoric acid is
Triprotic.
• Reacts with CHO’s
or alcohols to form
esters.
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Phosphoric Acid & Related Compounds
As found in DNA
& RNA at pH7
• Phosphoric acid is
Triprotic.
• Reacts with
alcohols to form
esters.
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The sugar may be Ribose (in RNA) or
Deoxyribose (in DNA)
H
Ribose
Deoxyribose
Phosphate can covalently bond to C3 and C5
Bases (A,C,G,T or U) can covalently bond to C1
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Bases in DNA and RNA
(RNA)
(DNA)
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A Base Joined To A Ribose Sugar
Is Called A Nucleoside
Purines bond N-9 to 1’ Carbon of sugar
or H
The carbons in the ribose are now
designated as C prime (or C’) to
distinguish them from those in the base.
Pyrimidines bond at N-1 to C-1’
or H
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When Phosphate is Bound to a Nucleoside it is
Called a Nucleotide
• ATP, GTP, CTP, UTP (NTPs) are substrates for RNA synthesis
• dATP, dGTP, dCTP, dTTP (dNTPs) are substrates for DNA synthesis
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Mononucleotides as they Occur in DNA & RNA
A,C,G or T (DNA)
or
A,C,G or U (RNA)
DNA
All nucleotides
are asymmetrical
RNA
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DNA & RNA are Polymers of Nucleotides
5’C =
3’C =
Four Nucleotides With
5’ to 3’ Phosphodiester
Linkages
All DNA and RNA
polymers are asymmetrical
with 5’ to 3’ direction.
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Properties of DNA and RNA
• They may be informational eg genomic DNA, mRNA.
• They may be structural eg rRNA & tRNA.
• Retain 5’& 3’ molecular orientation due to nucleotide asymmetry.
• They are often single stranded (typically RNA).
• They may be extremely long. Movie*
• Two polymers (or strands) may become double stranded when
certain conditions are met ie they are antiparallel &
complementary in nucleotide sequence (typically nuclear DNA).
* Terao et al., 2008: Lab on a chip DOI: 10.1039/b803753a
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Duplex DNA is Antiparallel
or
5’Phosphate
3’OH
3’OH
5’Phosphate
or
3’
5’
5’
3’
Duplex DNA is NEVER Parallel!
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Duplex DNA has Complementarity
because of Hydrogen Bonds
• H bonds are weak (~1/20th of a covalent bond):
– Often allows transient contact between molecules
(biological signalling systems).
– May allow stable contact that can be disrupted and
reformed (eg DNA).
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Hydrogen Bonds
• Form between O &/or N with H
between them
eg O-H…O, N…H-N or O-H…N.
• Are due to electrostatic forces.
H is slightly +ve.
O &/or N are slightly -ve.
• Are very weak compared to
covalent bonds
• May be broken & reform under
various chemical or physical
conditions.
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Two representations
of duplex DNA
showing:
• H bonds between
bases and,
• Covalently bonded
Sugar Phosphate
backbones.
• ~10 basepairs per
turn of the helix.
• Duplex DNA width
= 2nm.
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Double Stranded (or Duplex) DNA
• Is characteristic of genomic DNA.
• Consists of two separate nucleic acid polymers (“strands”).
• The two strands are Antiparallel wrt 5’& 3’ ends.
• They are held together by Hydrogen Bonds between the bases.
• H-Bond energies are weak BUT there are many of them which makes
the duplex DNA very stable.
• Bases are Complementary such that:
– A always pairs with T (2 H Bonds).
– C always pairs with G (3 H Bonds).
• Two strands of complementary antiparallel DNA form a Double
Helix eg as found in a chromosome.
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History of The Double Helix of DNA
• The structure of the double helix was found by
Rosalind Franklin using X-ray crystallography
and correctly interpreted by Watson & Crick in
1953 who also used Chargaff’s rule.
• The bases are Hydrophobic and are in the
Centre of the helix where complementary
bases pair via H-bonding.
• The Ribose Sugar and Phosphate groups
are on the Outside of the helix where they
can H bond to polar solvents like water.
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Key data that Watson & Crick worked with
Xray diffraction pattern of DNA similar to
Franklin’s data (above, 1953).
A G
C T
Chargaff’s Rule: there is a 1:1 ratio
of purines to pyrimidines (because
A=T, GC always).
1
Watson & Crick’s
structure for DNA
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