No abstract

Methyl methansulfonate UV sensitive clone 81 (Mus81) and essential meiotic endonuclease 1 (Eme1) form a heterodimeric endonuclease that preserves genomic integrity through the repair of DNA replication‐associated damage. Despite its role as genome guardian and tumour suppressor, our understanding of how this endonuclease is coordinated during the DNA damage response is poor. In order to identify other proteins that interact with Mus81‐Eme1, our laboratory conducted a protein interaction screen to identify and characterize proteins that interact with Eme1. One candidate identified in this screen was found to encode the carboxy‐terminal domain of Np95, a chromatin‐associated ubiquitin ligase. Np95 and Eme1 co‐localize on nuclear chromatin following exposure of cells to camptothecin, an agent that promotes the collapse of replication forks. The observed co‐localization following DNA damage was found to be dependent on an intact RING finger, the structural motif that encodes the E3 ubiquitin ligase activity of Np95. These findings for the first time, link the tumour‐suppressor Mus81‐Eme1 with the replication‐associated chromatin modifier functions of Np95 in the DNA damage response. Supported by grants from the Canadian Cancer Society through the National Cancer Institute of Canada and the Cancer Research Society.