DNA polymerase. is acetylated in response to SN2 alkylating agents

DNA polymerase iota (Pol iota) belongs to the Y-family of DNA polymerases that are involved in DNA damage tolerance through their role in translesion DNA synthesis. Like all other Y-family polymerases, Pol iota interacts with proliferating cell nuclear antigen (PCNA), Rev1, ubiquitin and ubiquitinated-PCNA and is also ubiquitinated itself. Here, we report that Pol iota also interacts with the p300 acetyltransferase and is acetylated. The primary acetylation site is K550, located in the Rev1-interacting region. However, K550 amino acid substitutions have no effect on Pol iota's ability to interact with Rev1. Interestingly, we find that acetylation of Pol iota significantly and specifically increases in response to S(N)2 alkylating agents and to a lower extent to S(N)1 alkylating and oxidative agents. As we have not observed acetylation of Pol iota's closest paralogue, DNA polymerase eta (Pol eta), with which Pol iota shares many functional similarities, we believe that this modification might exclusively regulate yet to be determined, and separate function(s) of Pol iota.