1 (2/24/04) - Mutations & DNA Repair

Mutations: Consequences for gene function

1. Indel = addition/deletion of nt. pair -> frameshift in coding region

2. Base substitution:

pur -> pur or pyr -> pyr = transition

silent, nonsense or missense in coding region

Sources of mutation/ Mechanism of repair

1. DNA polymerase errors (if proofreading function fails)

2. Tautomerization = keto <-> enol tautomer shift causes misspairing

• Base analog mutagens increase likelihood

Can be repaired by postreplication (mismatch) repair

3. Slipped mispairing during replication -> frameshift in coding region

or trinucleotide repeat diseases

• Base intercalation mutagens increase likelihood

4. Base damage = depurination and deamination

Can be repaired by excision repair pathway or recombination repair

Too much will induce SOS system -> "error-prone repair"

Mechanisms of mutagen action

1. Base replacement - analogs increase tautomerization rate

2. Base intercalation - insert in helix and cause indel lesion

3. Base damage - complementary information lost

4. Base alteration - chemical change in base that allows misspairing

5. DNA breakage