Functional relevance of interaction between Api5 and TopBP1

Abstract

Protein-protein interactions enable the cells to perform numerous functions. These interactions could enhance or reduce the levels/functions of the protein or even switch the role of the protein involved in the interaction. This study focuses on the functional relevance of the interaction between two proteins, namely Api5 and TopBP1, whose interaction strengthens upon DNA damage. One of the proteins was deregulated in this project, and the other protein’s levels were studied. Knockdown of Api5 led to the decrease of TopBP1 protein levels; however, the transcript levels remained unchanged. Induction of DNA damage dramatically decreased the levels of TopBP1. Overexpression of Api5 led to an increase in the levels of TopBP1, but the increase was not prominent following DNA damage. TopBP1 overexpression led to a slight enhancement in the protein levels of Api5 and the transcript levels. Earlier studies from this lab suggest that Api5 stability and functions are regulated by two main post-translational modifications (PTMs) following DNA damage: acetylation at Lys-251 and phosphorylation at Ser-138. PTMs could act as a trigger to change the protein's function, stability, and interacting partners; therefore, this project also aims to understand the role of the above-mentioned PTMs of Api5 on the Api5-TopBP1 interaction.