4) Exposure of DNA to oxidizing agents can result in the oxidation of G residues
ID: 191995 • Letter: 4
Question
4) Exposure of DNA to oxidizing agents can result in the oxidation of G residues in the DNA resulting in the formation 8-oxoG. This damage is highly mutagenic since 8- oxoG can pair with A, which leads to a G to T transversion mutation. This type of mutation frequently occurs in tumor suppressor genes such as p53 leading to cancer. The 8-oxoG:A H2N basepair has the structure shown on the right. Note that this basepair can only form if the glycosidic bond to the 8-oxoG is in the syn conformation. dR dR Why does the glycosidic bond to 8-oxoG prefer the syn conformation? Answer in the online text field. a. b. As implied by question #3, non-Watson/Crick basepairs are usually rejected by DNA polymerase. How does this non-Watson/Crick basepair (the 8- OxoG:A basepair) "fool" the enzyme leading to inappropriate nucleotide addition? Answer in the online text field.Explanation / Answer
a. 8-oxoG favors a syn-conformation that can form Hoogsteen base pair with adenine. This glycosidic torsion angle preference is due to steric repulsion between O8 and deoxyribose.
b.There are two main characteristics for the recogniton of a correct watson-crick base pair by DNA polymerase.
1. two H-bonds are required for exact recognition.
2. recognition from the minor groove side is relatively insensitive to base pair reversals
High accuracy in replication are achieved through three main processes: polymerase selectivity, proofreading and mismatch repair.
Non-watson crick base pair
Non-watson crick base pair are recognised by DNA polymerase by mismatch or lack of accuracy.This lack of accuracy is due to competition between the correct G·C/A·T base pairs and eight possible mismatches : A·A, G·G, A·G, C·C, T·T, C·T, A·C and G·T. The first three of these mispairs (A·A, G·G and A·G) are purine-purine mismatches; the second three (C·C, T·T and C·T) are pyrimidine-pyrimidine mismatches; and the other two (A·C and G·T) are purine-pyrimidine mismatches.
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