1. DNA Mutation

2. DNA mutations are Unavoidable
What are advantages and disadvantages of DNA mutations?
Advantages
Diversity
Evolution/Adaptations
Beneficial mutations
Disadvantages
Cell death
Genetic diseases

3. Cause of DNA Mutations 1. Tautomeric Shift 2. Replication Slippage
3. Base Analogs
4. Alkylation
5. Deamination
6. Abasic Sites
7. Intercalating Agents
8. Radiation

4. DNA replication Errors
DNA replication errors can occur through the following primary mechanisms:
Tautomeric Shifts
Replicating repeated sequences
Figure 16.3b Genomes 3 (© Garland Science 2007)

5. Tautomeric Shift

6. Tautomeric Shift
“Tautomeric shifts” ie. spontaneous rearrangements of the nitrogen bases. These arrangements allow for hydrogen bonding of mismatched base pairs.

8. DNA Polymerase Slippage
Errors made by replicating repetitive sequences. These sequences are called DNA microsatellites. (Mono-, Di-, Tri-, Tetranucleotide Repeats)
DNA polymerase “stalls” at these sites.
DNA polymerase stalls is associated with base pairing of the repetitive sequence. This can cause either deletions or insertions.
DNA Strand Slippage Model

9. DNA Replication Errors: Repetitive Sequences
2. Slippage
DNA polymerase stalls
Sequence is not copied on the newly synthesized strand!

11. Many neurological conditions are caused by DNA replication errors due to repetitive sequences
II. DNA Replication Errors
Slippage

12. Non-Replication Dependent Damage
Mutagens—Lots of different types of mutagens
Base Analogs
Alkylating agents
Abasic Site
Deamination
5. Radiation

14. Base Analogs 5-Bromouracil
Used as a mutagen to make A-T to G-C transitions
Tautomeric shift

17. Alkylation and
Deamination

18. Abasic Sites

19. Intercalating Agents

21. Radiation
-T-T dimers, major product

22. Ionizing Radiation Ionizing radiation induced double-stranded breaks
X-rays
From Slide-Player
Ionizing –remove electrons

23. Double-stranded Breaks
dsDNA breaks are caused:
Directly, by ionizing radiation or other DNA damaging reagents
If unrepaired, they can result in Chromosomal Abnormalities