DNA Mutation.

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Presentation transcript:

DNA Mutation

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

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

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)

Tautomeric Shift

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

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

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

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

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

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

Alkylation and Deamination

Abasic Sites

Intercalating Agents

Radiation -T-T dimers, major product

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

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