7.2 Molecular mechanisms of mutation Flashcards
What corrects mutations/base changes
DNA repair
true or false: there is a race between DNA repair and DNA replication
true. DNA repair occurs before DNA replication, before the mutation is incorporated into the genome
What are the 8 natural processes that cause spontaneous mutatons through DNA damage
- Depurination
- Deamination
- X-rays
- Ultraviolet light
- Oxidative damage
- Proofreading
- Base tautomerization
- Trinucleotide repeats
What is depurination
is a process in which a purine base (adenine or guanine) is lost from a DNA molecule due to the breaking of the glycosidic bond between the base and the sugar. This leaves an empty site in the DNA strand called an AP (apurinic) site. If not repaired, this can lead to mutations during DNA replication, as DNA polymerase may insert an incorrect base opposite the missing site. Depurination is one of the most common types of spontaneous DNA damage. it happens 1000/hr in every cell
What is deamination of C
The removal of an amino group (-NH2). It changes cytosine to uracil. Hence, deamination followed by replication may alter a C:G base pair to a T:A pain in future generations of DNA molecules.
Explain X rays
naturally occuring radiation which breaks the sugar phosphate backbone of a DNA molecule
Explain ultraviolet light
It causes adjaent thymine residues to become chemically linked into thymine dimers (DNA lesions formed when two adjacent thymine bases bond covalently)
Explain oxidative damage
(of any of the four bases)
8-oxodG(Guanine) mispairs with Adenine
so normal G-C becomes mutant A-T after replication
Explain Proofreading (function of DNA polymerase)
It decreases mistakes during replication. Proofreading function of DNA polymerase—3’-to-5’ exonuclease recognizes and excises mismatches. Mutations may occur if the polymerase misses an error, allowing it to remain uncorrected, or if it mistakenly removes a correct nucleotide and replaces it with an incorrect one. Additionally, in regions of repetitive sequences, polymerase slippage can lead to insertions or deletions, causing frameshift mutations if not corrected. Though proofreading is generally protective, these rare events highlight its potential to introduce mutations.
Explain what Base tautomerization
Another reason DNA polymerase may make mistakes is due to base tautomerization. Each of the 4 bases has two tautomers (similar chemical forms that interconvert continually). This causes mutations when DNA bases temporarily shift to alternative forms, or tautomers, with slightly different structures. These rare forms change the base-pairing properties: for example, adenine may pair with cytosine instead of thymine. If a tautomeric form occurs during DNA replication, the incorrect base pairing can result in the incorporation of the wrong nucleotide. When DNA replicates again, this mismatch becomes a permanent mutation, introducing an error into the DNA sequence (point mutations)
Explain how trinucleotide repeats cause mutation
Trinucleotide repeats are sequences in DNA where a three-nucleotide motif (like CAG) repeats multiple times. During DNA replication, slippage by DNA polymerase in these regions can lead to mutations by changing the repeat count. Repeats above/under a certain number result in disease causing alleles
Differentiate between expansion and contraction of trinucleotide repeats
Expansion: When slippage causes the repeat number to increase (e.g., CAG becomes longer), it results in more repeated motifs. This can lead to disorders if the repeat count exceeds a certain threshold (e.g., Huntington’s disease).
Contraction: When the slippage reduces the repeat count, it’s called contraction, leading to fewer repeats than the original sequence. While less common, it can still impact gene function if repeats are critical for normal expression.
What is a mutagen
It is a physical or chemical agent that raises the frequency of mutations above the spontaneous rate.
What are the three ways in which mutagens alter DNA (chemical action)?
- Replace a base
- Alter base structure and properties:
a) Hydroxylating agents add an -OH group
b) Alkylating agents add ehtyl or methyl groups
c) Deaminating agents remove amine groups - Insert between bases: Intercalating agents- cause double strand breaks
What are the four accurate repair systems
- correction of DNA replication errors
- Double-strand break repair
- Reversal of DNA base alterations (excision repair)
- Homology-dependent repair of damaged bases or nucleotides
