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Molecular Biology
CHM6640/7640
Lecture #2
“Structure of DNA and RNA”
Presented by Joanna Klapacz
For Dr. Ashok S. Bhagwat
Thursday January 10, 2008
Nucleic Acids:
• 2 major types: DNA and RNA
• Molecular repositories of genetic information in cells
• Variety of other roles in cellular metabolism:
• energy currency of metabolic transactions
• messengers in signaling pathways
• components of enzyme cofactors
1. Nucleotides are the building blocks/polymers of nucleic acids.
2. Nucleotides are composed of three parts:
• Nitrogen containing base
• Pentose sugar moiety
• Phosphate group
3. Nucleoside is composed of base + sugar.
or 2’-H
Default
or 2’-H
Structures of Adenosine Monophosphates
Found in DNA and RNA: Found in RNA only:
O
HN C
OH
N C
keto enol
NH
HN C
NH2
N Camino imino
>10,000 : 1
Keto and Amino Groups in Bases Can Undergo Rearrangements.
Resonance Structure of Bases
Keto- and Amino groups in bases can undergo rearrangements.
Predominant Forms
Could Lead to Base Mispairing
Chemical Properties of Nucleic Acids
If pH is <4 or >10 in solution, the base pairs are disrupted because of protonation/deprotonation of keto and amino groups.
Site Affected pKa
Adenylate N1 3.9Guanylate N1 10.0Cytidylate N3 4.5Thymidylate N3 10.5Adenylate N7 2.4Guanylate N7 2.4
B-Form DNA
• Defined by Watson-Crick base pairing.• Most stable structure of DNA under physiological conditions.
Specialized Structure in Nucleic Acids
: read identically either forwards or backwards
Regions of DNA with inverted repeats that are self-complementary.
DISEASE
CELL DEATH
Mutation
Cell cycle arrest
DNA REPAIR
Certain chronic or metabolic diseases
CH3
Alkylating Agents Occur Ubiquitously
and Cause DNA Damage
Endogenous
Environmental
Man-made
Alkylating Agents
Bi-functional/Cross-Linking
SN1 Alkylating Agent
SN2 Agent
SN1 Alkylating Agents
* Alkylating Agents used clinically as chemotherapeutics
Model
Mono-functional
Bi-functional
Wyatt and Pittman. 2006. Chem. Res. Toxicol. 19:1580-94
DNA Methylating Agents Induce More than a Dozen Different Lesions in DNA
Other targets• phosphotriesters• deoxyribose
Filled Arrows: SN1Empty Arrows: SN1 and SN2
O6-methylguanine is Mutagenic
Cytosine Guanine
N
N
N HH
OdR
N
N N
N
dR
O
H
NHH
Thymine O6-methylguanine
N
N
O
OCH3
dR
H
N
N N
N
dR
O
NHH
CH3