RNA metabolism proteins identified as ATM and 53BP1 partners function in the DDR

Abstract

The DNA is continually under treat of being damaged by both endogenous and exogenous sources such as reactive oxygen species produced during normal cell metabolism or ionising radiation. It is vital for the maintenance of genome integrity that cells deal with such damage efficiently and faithfully. The most deleterious lesions of the DNA are double strand breaks and the cell has developed to main repair pathways, homologous recombination and non-homologous end-joining, in order to deal with such damage.

In this study we are investigating the role of three RNA metabolism proteins, DGCR8, DDX3X and DDX17, in the DDR. These proteins were identified in recent proteomic screens as potential interacting proteins of ATM and 53BP1, respectively.

We demonstrate that DDX3X is a novel interacting partner of ATM and is required for efficient DNA repair by homologous recombination. We also investigate the role of DGCR8 in the DNA damage response independent of its partner protein Drosha. We propose that DGCR8 has a potential role in regulating ATM kinase activity. In addition to these two ATM interacting proteins, we have also identified DDX17 as a novel 53BP1 interacting partner involved in DSB repair by both homologous recombination and non-homologous end-joining.