DNA Repair Flashcards
1
Q
contrast DNA damage and DNA mutation
A
- DNA damage is repaired
- DNA mutation becomes part of that DNA
2
Q
name the 2 classes of spontaneous mutation
A
- Error of replication = mistake made during replication
- only occurs during S phase of cell division
- Spontaneous lesions = spontaneous chemical changes
- occurs in resting cell
3
Q
describe the process in error of replication
A
- wrong base is incorporated by DNA polymerase due to chemistry of the nucleotides
- Tautomerism = the ability of certain chemicals to exist as a mixture of 2 interconvertible isomers
- Thymine and the rare enol form that pairs with G
4
Q
describe Bloom syndrome
A
- Defect in BLM gene
- a DNA helicase enzyme
- this defect leads to chromosomal instability resulting in many chromosomal breaks and sister chromatid exchanges
- higher risk of a broad range of cancer types
5
Q
describe Fanconi anemia
A
- an AR disorder
- etiology: multiple genes involved (A-H, all related to DNA repair)
- locus heterogeneity
- increased spontaneous chromosome breakage which is made worse by exposure to DNA cross linking agents
- significant increased risk of neoplasia
6
Q
describe and name the 3 types of spontaneous lesions
A
- changes that occur in a resting cell due to the chemical nature of the DNA
- extremely common – tens of thousands of damage events/cell/day
- 3 types
- depurination
- deamination
- oxidative damage
7
Q
describe depurination
A
- most common form of spontaneous lesion
- process:
- breaking of glycosidic bond between base and sugar in purine nucleotides
- sugar-phosphate backbone reamins but base is lost
- becomes an apurinic site
- if it persists through replication then mutation can occur
8
Q
describe deamination
A
- loss of amine group from base (particularly cytosine)
- cytosine deaminates to form uracil
- uracil would like to pair with A
- this one is easy to fix – Uracil does not belong in DNA
-
However, another type can occur
- 5-methyl cytosine deaminates to thymidine
- T-G pair
- both normal bases and could be repaired to TA or CG
- mutational hotspot
9
Q
describe oxidative damage
A
- a result of the production of reactive oxidative compounds due to oxidative metabolism
- superoxides, peroxides
- cause oxidative damage to many parts of cell including addition of oxygen groups to nucleotide bases
- results in mispairing with A and potential transversion
10
Q
describe the effects of UV light on DNA
A
- generates deleterious photoproducts like pyrimidine dimers
- leads to covalent linkages between bases on the same strand
- interferes with normal pairing and block replication
- These are known as pyrimidine dimers or thymine dimers
11
Q
describe nucleotide excision repair mechanism
A
- process:
- recognition of damage
- recruit endonucleases
- region excised
- DNA pol fills in gap
- Ligase seal nick
- this is how pyrimidine dimers formed by UV damage are repaired
12
Q
describe Xeroderma pigmentosum (XP)
A
- autosomal recessive, mutations in 9 different NER genes can produce XP
- extreme sun sensitivity
- sunburn, blistering
- 1000 fold increase in skin cancer including melanomas
- DNA damage is cumulative and irreversible
13
Q
describe base excision repair
A
- damaged nucleotides can be removed by DNA glycosylases which recognize specific damaged bases in DNA
- this fixes damaged bases by removing it (damage by methylation, oxidation, etc)
14
Q
describe mismatch repair
A
- post-replicative repair mechanism
- can fix damage caused by tautomerisms
- a form of excision repair
- same basic mechanism but different proteins involved
- important in relation to removing small repeats that tend to expand (triplet expansion disorders)
15
Q
describe the mismatch repair process
A
- mismatch missed by proofreading is recognized by MMR proteins
- repair may occur during S-phase (if missed by proofreading) or in G2 when genome is scanned for errors
- excision of bases around mismatch
- repair by resynthesis
