Mutations & DNA Repair. What are mutations? Mutagenesis: Process of producing a mutation Repair of mutations. Mutations can cause changes in the shape of a protein which alters its function. What are mutations?. Classes of mutations:
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Mutations can cause changes in the shape of a protein which alters its function.
T & C
A & G
-Breaks in DNA strands
-Damage to nucleic acids
II. Mutagenesis: Process of producing a mutation
a) Tautomeric Shifts - Tautomerization – isomerization of a nitrogen base to an alternative H-bonding condition
5-Bromocuracil (T analog),
2-Aminopurine (A analog)
“rare” forms result in mispairing,
Mispairing results in replication errors – the wrong bases are incorporated into the daughter strands
5 BU (derivative of uracil) behaves as a thymine analog, if 5 BU is incorporated it will base pair with guanine, after 1 round of replication an A-T to G-C transition results
EMS alkylates the keto groups of G and T, base pairing is altered and a transition results
Intercalating agents slip between the nitrogenous bases, which can lead to insertion/deletions.
Frameshift mutations result – generated at gaps produced in DNA during replication
Photoreactivation repair: reversal of UV damage
O6-mGua DNA methyltransferase
Alkyltransferase – one time repair enzyme that removes ethyl or methyl groups from guanine
Involved in repair of deamination and depurination
Enzymes recognize an abnormal base and cleave the bond between in and the sugar in the DNA backbone.
DNA Pol III error rate: 10-5
Important to recognize difference between old strand & new strand:
If mutated base excised, the wild type is restored, but if the original wild type is excised, the mutant sequence becomes fixed.
Post-replicational repair (aka recombination repair ):