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Mutations and mutagens
Transitions and transversions
A G
T C
transition
transition
transversions
Causes of transitions
Agent (mutagen, etc.) Example Result
Nucleotide analogs BrdUTP transitions, e.g. AT to GCOxidizing agents nitrous acid transitions, e.g. CG to TAAlkylating agents nitrosoguanidine transitions, e.g. GC to AT
Causes of transversions
Misincorporation:Altered DNA Pol III mutD=dnaQ; subunit of DNA PolIII
transitions, transversions and frameshifts in mutant strains
Agent Example
Result
UV radiation generates pyrimidine dimers
Ultraviolet radiation (260 nm)
a) Causes pyrimidine dimers between adjacent pyrimidines. The dimers can be of two types :
1) The major product is a cytobutane- containing thymine dimer (between C5 and C6 of adjacent T's)2) The "6-4" photoproduct is also formed, and this causes the major mutagenic effect
b) The pyrimidine dimers cause a distortion in the DNA double helix
c) The dimers block replication and transcription
Structure of pyrimidine dimers
N
HN
H
O
O
CH3
Thymine
N
HN
H
O
O
CH3
Thymine
d-ribose d-ribose
55
6 6 (lose double bond; add H to C6)
Another view of cyclobutane pyrimidine dimers in DNA
N
N
O
H
O
O H
HO
O
H3CN
N
O
H
O
HO H
O
O
H3C
P
O
-O
45
6
cyclobutane thymine dimers in DNA
5
6
1 2
4
3
6-4 photoproducts of thymine dimers
N
N
O
H
O
O H
HO
O
H3C
6-4 photoproducts of thymine dimers in DNA
5
6
N
NO
HO H
O
O
H3C
5
6
P
O
-O
4
4
1 2
3
