Title: DNA Damage: DNA Adducts, Mutations, Mechanisms of Mutagenesis
1DNA Damage DNA Adducts, Mutations, Mechanisms of
Mutagenesis
- Prof. Avram Gold
- Rosenau 157
- 966-7304
- golda_at_email.unc.edu
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4PAIRING SCHEME OF DNA BASES AND DIRECTIONALITY OF
DNA STRANDS and also appropriate nomenclature
nucleobases guanine (Gua, G) adenine (Ade,
A) cytosine (Cyt, C) thymine (Thy,
T) nucleosides (deoxy-) guanosine (dGuo,
dG) adenosine (dAdo, dA) cytidine (dCyd,
dC) thymidine (dThyd, dT) nucleotides
(deoxy-) guanylic acid adenylic acid cytidylic
acid thymidylic acid
5Ribbon representation of DNA
minor groove
major groove
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7FUNCTIONS OF DNA
- REPLICATION
- 1. DNA stores and passes on genetic information
which consists of codes for amino acids and their
sequence in proteins. The information is coded
by the arrangement of nucleobases in groups of
three, called triplets or codons, where each
codon represents an amino acid. - TRANSCRIPTION
- 2. DNA is also used for translating genetic
information into the proteins necessary for
organisms to grow and survive.
8http//highered.mcgraw-hill.com/sites/0072437316/s
tudent_view0/chapter14/animations.html
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10Methylation at O6 of dGuo and O4 of dThyd results
in instructional lesions that lead directly to
mis-pairing of bases and a base pair substitution
mutation when the strand bearing the wrong
partner is a template for replication
H
Keto-enol tautomerization of guanine
11FIXING A MUTATION
One round of replication on mismatched strands
fixes the mutation.
GT GT AT
CLASSES OF POINT MUTATIONS
Point mutation, transition pyrimidine?pyrimidine p
urine?purine
GC AT AT GC
Point mutation, transversion pyrimidine?purine pur
ine?pyrimidine
GC CG, TA AT, GC TA
nonsense mutation occurs when a termination codon
is generated missense mutation occurs when a
different amino acid is coded
12FRAME SHIFT MUTATIONS
ATC GCT TAA TTC GCA CCT TAC TA
-1 frameshift
delete G
ATC GGC TTA ATT CGC ACC TTA CTA
wild type
insert G
ATC GGG CTT AAT TCG CAC CTT ACT A
1 frameshift
13Mechanism for frameshift mutations
G-p
3'-G-p-G-p-G-p-G-p-G-p-G-5' 3'-G-p-G-p
G-p-G-p-G-p-G-5' 5'-C-p-C p-C-OH 5'-C-p-C-p-C-O
H
p-C
insertion
deletion
14CATEGORIES OF DAMAGE
1. Bulky covalent adducts. 2. Sterically benign
covalent adducts (do not distort DNA). 3.
Alteration of nucleobase structure without
formation of covalent adducts.
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