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The defective or incorrect base is removed by a dna

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Unformatted text preview: The defective or incorrect base is removed by a DNA glycosylase. Several di erent DNA glycosylases recognize di erent problem bases. 1. This structure shows UDG bound to a DNA duplex containing a dU:dG mismatch. 2. The backbone is cleaved at the AP site by AP endonuclease. 2. It shows the state of the enzyme:substrate complex immediately after hydrolysis of the glycosidic bond. 3. A gap is made on the defective strand by an exonuclease. 4. The second strand is used as a template to ll in the gap. This process is carried out by a DNA polymerase and a DNA ligase. 3. Note the base- ipping mechanism of the enzyme! AP site AP = abasic (apurinic or apyrimidinic) 4. Note distorted DNA backbone Note that this mechanism provides a rationale for why dT - not dU - is found in DNA: the excision repair machinery “knows” that when dU is present, it is almost certainly the product of deamination of dC! * also known as a DNA glycosidase 13 Type of Damage Base misincorporation (e.g., from tautomerization) Proofreading DNA polymerases with 3´→5´ exonuclease activity Direct Repair DNA ligase Single-strand DNA nicks (radiation; spontaneous hydrolysis) UV photoproducts: cyclobutane pyrimidine dimers; 6-4 photoproducts Direct Repair 14 To do di erent jobs, di erentiated cells must make di erent proteins in di erent places. Summa...
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