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Repair Of O6-Methylguanine Adducts In Human Telomeric G-Quadruplex Dna By O6-Alkylguanine-Dna Alkyltransferase, Lance M. Hellman, Tyler J. Spear, Colton J. Koontz, Manana Melikishvili, Michael G. Fried

Molecular and Cellular Biochemistry Faculty Publications

O⁶-alkylguanine-DNA alkyltransferase (AGT) is a single-cycle DNA repair enzyme that removes pro-mutagenic O⁶-alkylguanine adducts from DNA. Its functions with short single-stranded and duplex substrates have been characterized, but its ability to act on other DNA structures remains poorly understood. Here, we examine the functions of this enzyme on O⁶-methylguanine (6mG) adducts in the four-stranded structure of the human telomeric G-quadruplex. On a folded 22-nt G-quadruplex substrate, binding saturated at 2 AGT:DNA, significantly less than the ~ 5 AGT:DNA found with linear single-stranded DNAs of similar length, and less than the value found with the …