Are Bases Alkylated by Branched Alkylating Agents Removed by Nucleotide Excision Repair or Base Excision Repair?

Abstract

We have shown that comet-positive responses by adducts that are repaired by nucleotide excision repair (NER) and base excision repair (BER) are reduced by α-amanitin (AMN) and enhanced by 2’, 3’-dideoxythymidine (ddT), respectively. Based on this finding, bases alkylated by n-alkyl groups with ≦5 carbons and those with ≧4 carbons were discussed to be removed by BER and NER, respectively. To study whether bases alkylated by branched alkyl groups can be removed by NER or BER, 4 alkyl methanesulfonates that have a branched methyl group with different branching positions [iso-propyl methanesulfonates (iPMS), 1-methyl-pentyl methanesulfonate (1MPeMS), 2-methyl-pentyl methanesulfonate (2MPeMS), and 3-methyl-pentyl methanesulfonate (3MPeMS)] were synthesized. We studied the reduction of comet-positive responses by AMN and their enhancement by ddT for those alkyl methanesulfonates with a branched methyl group