Mutations and mutagens. Transitions and transversions.

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