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==General Function== | ==General Function== | ||
[[1diz]] Escherichia coli 3 methyladenine DNA glycosylase II (AlkA), shown as a dimer, is a DNA repair enzyme that initiates base excision repair for the removal of alkylated bases. There are many environmental toxins and cellular agents that may alkylate DNA bases. One example is Aflatoxin, a compound that is converted into a reactive epoxide by cytochrome P450 and attacks guanosine at its N-7 atom to form an alkylated base.<ref name="Berg">Berg, Jeremy, Tymoczko John, and Lubert Stryer. Biochemistry. 6th. New York: W.H. Freeman and Company, 2007. 806-808. Print. </ref> The alkylated DNA bases prevent regulatory proteins from binding to DNA and blocks replicative polymerases to stop DNA synthesis.<ref name="Hollis">Hollis, Thomas, Yoshitaka Ichikawa, and Tom Ellenberger. "DNA bending and a flip-out mechanism for base excision by the helix-hairpin-helix DNA glycosylase, Escherichia coli AlkA." EMBO Journal. 19.4 (2000): 758-766. Print. </ref> AlkA initiates base excision repair by first locating and binding to the alkylated DNA. It has broad substrate specificity and is able to remove a variety of different alkylated bases. AlkA then flips the affected base out of the DNA double helix and into the active site of the enzyme. Once in the active site, AlkA hydrolyzes the glycosidic bond to release the damaged base and leave the sugar phosphate backbone intact. This creates the AP site that is either devoid of a purine or pyridine. The AP site signals to other base excision repair enzymes to insert an undamaged nucleotide based on the undamaged complementary strand and seal the DNA.<ref name="Berg">Berg, Jeremy, Tymoczko John, and Lubert Stryer. Biochemistry. 6th. New York: W.H. Freeman and Company, 2007. 806-808. Print. </ref> | [[1diz]] ''Escherichia coli'' '''3 methyladenine DNA glycosylase II''' (AlkA), shown as a dimer, is a DNA repair enzyme that initiates base excision repair for the removal of alkylated bases. There are many environmental toxins and cellular agents that may alkylate DNA bases. One example is Aflatoxin, a compound that is converted into a reactive epoxide by cytochrome P450 and attacks guanosine at its N-7 atom to form an alkylated base.<ref name="Berg">Berg, Jeremy, Tymoczko John, and Lubert Stryer. Biochemistry. 6th. New York: W.H. Freeman and Company, 2007. 806-808. Print. </ref> The alkylated DNA bases prevent regulatory proteins from binding to DNA and blocks replicative polymerases to stop DNA synthesis.<ref name="Hollis">Hollis, Thomas, Yoshitaka Ichikawa, and Tom Ellenberger. "DNA bending and a flip-out mechanism for base excision by the helix-hairpin-helix DNA glycosylase, Escherichia coli AlkA." EMBO Journal. 19.4 (2000): 758-766. Print. </ref> AlkA initiates base excision repair by first locating and binding to the alkylated DNA. It has broad substrate specificity and is able to remove a variety of different alkylated bases. AlkA then flips the affected base out of the DNA double helix and into the active site of the enzyme. Once in the active site, AlkA hydrolyzes the glycosidic bond to release the damaged base and leave the sugar phosphate backbone intact. This creates the AP site that is either devoid of a purine or pyridine. The AP site signals to other base excision repair enzymes to insert an undamaged nucleotide based on the undamaged complementary strand and seal the DNA.<ref name="Berg">Berg, Jeremy, Tymoczko John, and Lubert Stryer. Biochemistry. 6th. New York: W.H. Freeman and Company, 2007. 806-808. Print. </ref> | ||