LIM Protein Ajuba associates with the RPA complex through direct cell cycle-dependent interaction with the RPA70 subunit

Authors

Sandy Fowler, CUNY Hunter CollegeFollow
Pascal Maguin, CUNY Hunter College
Sampada Kalan, CUNY Hunter CollegeFollow
Diego Loayza, CUNY Hunter CollegeFollow

Document Type

Article

Publication Date

6-22-2018

Abstract

DNA damage response pathways are essential for genome stability and cell survival. Specifically, the ATR kinase is activated by DNA replication stress. An early event in this activation is the recruitment and phosphorylation of RPA, a single stranded DNA binding complex composed of three subunits, RPA70, RPA32 and RPA14. We have previously shown that the LIM protein Ajuba associates with RPA, and that depletion of Ajuba leads to potent activation of ATR. In this study, we provide evidence that the Ajuba-RPA interaction occurs through direct protein contact with RPA70, and that their association is cell cycle-regulated and is reduced upon DNA replication stress. We propose a model in which Ajuba negatively regulates the ATR pathway by directly interacting with RPA70, thereby preventing inappropriate ATR activation. Our results provide a framework to further our understanding of the mechanism of ATR regulation in human cells in the context of cellular transformation.

Comments

This article was originally published in Scientific Reports, available at DOI:10.1038/s41598-018-27919-8.

This article is licensed under a Creative Commons Attribution 4.0 International License.