Biochemistry 2280A Final: Topic 21- DNA repair

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Topic 21: DNA Repair
TYPES OF DNA DAMAGE:
DNA damage: changes in the sequence or structure of DNA
1. Copying mistakes
- mistakes occur during DNA replication at a rate of 1 per 10^7 nucleotides in
humans
-on or more mismatched bp leads to a change in the DNA sequence = mutation
after replication
2. Depurination
-acid promotes the loss of an entire A or G base. Results in abasic site.
-sugar-phosphate backbone remains intact
-abasic sites block replication
-when polymerase stalls, one translesion DNA polymerases is recruited to the site.
-translesion DNA polymerase: able to synthesize DNA past the site of damage, but
b/c the template has no base, they are likely to EITHER:
a) skip the position
b) introduce a mutation in the newly synthesized strand
-After a translesion polymerase has synthesized DNA past the site of damage, the
normal replicative DNA pol resumes DNA synthesis
3. Deamination
-amine group of base (mostly cytosine) is changed to a carbonyl.
-Occurs spontaneously,
-upon deamination, cytosine uracil
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4. Pyrimidine dimers
-double bonds in adjacent pyrimidines (mostly 2 thymines) react to form a
cyclobutane ring
-usually caused by UV radiation
-translesion DNA polymerases are required to replicate DNA past pyrimidine
dimers, but are more error-prone than normal replicative dNA polymerases
INCREASING RISK OF MUTATION
5. Other base modi)cations
-ionizing radiation (X-rays, gamma rays) causes modi;cations to all four bases.
-mutagens react with DNA bases, leading to:
a.) changes in base-pairing properties
b.) stalled replication
-mutagen ex. (O2-)
6. Strand breaks
-mechanical stress/radiation can break sugar-phosphate backbone.
- can be either a single strand break or a double strand break
-DNA polymerase nor translesion polymerase can synthesize DNA past a break in
the template.
-Double strand breaks can cause:
a. chromosomal abnormalities
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