DNA polymerase ? is acetylated in response to SN2 alkylating agents.

ABSTRACT: DNA polymerase iota (Pol?) 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? interacts with proliferating cell nuclear antigen (PCNA), Rev1, ubiquitin and ubiquitinated-PCNA and is also ubiquitinated itself. Here, we report that Pol? 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?'s ability to interact with Rev1. Interestingly, we find that acetylation of Pol? significantly and specifically increases in response to SN2 alkylating agents and to a lower extent to SN1 alkylating and oxidative agents. As we have not observed acetylation of Pol?'s closest paralogue, DNA polymerase eta (Pol?), with which Pol? shares many functional similarities, we believe that this modification might exclusively regulate yet to be determined, and separate function(s) of Pol?.

SUBMITTER: McIntyre J 

PROVIDER: S-EPMC6423139 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature