DNA Repair: Lect 16 Flashcards
1
Q
DNA damage:
- short term consequences;
- long term consequences;
A
- in thousands of cells per day
- due to basic chemistry of nucleic acids, UV light, chemicals, radiation, pH, smoking.
- reduced proliferation, altered gene expression and cell death.
- aging and diseases (cancer).
2
Q
Molecular basis of mutation:
A
- Spontaneous or induced
- induced mutations increase rate of spont mutations.
3
Q
Two classes of Spontaneous mutation:
A
- Errors of replication: mistakes made during replication.
- only occurs during S-phase
- wrong base incorporated by DNA poly.
- Tautomerism - Spontaneous lesions: chemical changes that occur spontaneously.
- occurs in resting cell/during replication.
4
Q
Proof reading:
A
- a DNA repair mechanism
- slows down replication rate in order for the DNA to be checked.
- DNA poly has a 5’ to 3’ polymerase activity and a 3’ to 5’ exonuclease activity.
5
Q
Bloom syndrome:
A
defect in BLM gene
- DNA helicase required for replication repair and recombination.
- Chrom instability resulting in many chrom breaks and sister chromatids exchanges.
- higher risk of cancer
Characteristics:
- smaller than average, narrow chin, prominent nose and ears, facial rash upon sun exposure.
- Diabetes, neurological, lung and immune syst deficiencies.
6
Q
Fanconi anemia
A
- AR rare disorder
- multiple genes involved “locus heterogeneity”
- inc. spontaneous chrom breakage made worse by exposure to DNA cross linking agents.
- inc. risk of neoplasia.
Char:
-radial ray defects, pancytopenia, mental development problems, short stature.
7
Q
Frameshift mutations:
A
- tends to occur at positions where there are base repeats (GTCGAAAAACTCA)
- DNA loops or kinks at these points and one or more bases are not copied or are copied twice.
8
Q
Spontaneous lesions
A
- changes in resting cell
- extremely common
- increased by exposure to mutagens (sunlight).
- 3 main types
9
Q
3 types of Spont. lesions:
A
- depurination:
- most common; breaking of glycosidic bond btwn base and sugar in purine nucleotides.
- sugar-phosphate remains but base is lost. - deamination:
- very common; loss of amine grp from base cytosine
- cytosine deaminates to form uracil but uracil is not in DNA; so easy to fix.
- if 5-Me-cytosine deaminates to thymidine = mutational hotspot. - oxidative damage:
- from production of reactive oxidative compounds due to oxidative metabolism. (superoxides, peroxides)
- addition of oxygen groups to nucleotide bases
- result in potential tranversion
10
Q
Mutagens
A
- increase the frequency of nl mutations. (mismatches, depurinations)
- UV, ionizing radiation, aflatoxin, benzene, formaldehyde, mustard gases (serious ones)
11
Q
Ionizing Radiation
A
- X-rays and radioactive particles.
- high energy particles or rays can cause many types of cellular damage and apoptosis.
- damage to DNA and heritable mutations.
12
Q
UV light
A
- generates several deleterious photoproducts.
- interfere w/ normal pairing and block replication
- pyrimidine dimers or thymine dimers.
13
Q
Spontaneous DNA lesions?
A
most often have apurinic sites.
14
Q
Indirect DNA Repair
A
Nucleotide excision:
- removes more than a few base (~30) around damaged site.
- repairing of pyrimidine dimers from UV damage.
Base excision:
- repairs a single or few damaged bases by removing it
- methylation or oxidation damage
Mismatch Repair:
- post replication repair
- repairs mismatched bases from tautomerism.
15
Q
Excision repair mechanism:
A
- recognition of damage
- removal of damaged base or region around damaged base via endonucleases.
- replacement of excised region; DNA poly fills in gap and Ligase seals it.
