Analysis of Quasi-Palindrome Template-Switch Mutations after treatment with FDA approved drugs in E. coli

Abstract

Quasi-Palindromes (QP) are imperfect inverted repeats of DNA sequences with the ability to form secondary structures that block the DNA replication fork during DNA synthesis. These structures can cause mutations that have been associated with a variety of genetic diseases. If the DNA replication fork is blocked by QP structures, the main replicative protein, DNA polymerase, can use an alternative method to continue DNA replication, called “template-switching”, which results in a perfect palindrome, synthesized from a quasi-palindromic sequence. Although this is an efficient method, it is known to be mutagenic. It has been shown that template-switch mutations have been promoted after treatment of various well-known drugs such as 5-Azycatidine, an FDA-approved chemotherapy treatment, Azidothymidine (AZT), an antiviral chain terminator, and drugs that inhibit the action of topoisomerase II. The goal of this research project is to establish cellular consequences of additional FDA-approved drugs in QP mutations using E. coli as the model organism. We aim to understand the repercussions of additional drugs in template-switching QP mutations to increase our knowledge of the potential side effects for current FDA-approved drugs. Data from this research can be used to consider susceptibility of QP mutations when approving new drugs.