Sumo-mediated recruitment allows timely function of the Yen1 nuclease in mitotic cells

Abstract The modification of DNA damage response proteins with Sumo is an important mechanism to orchestrate a timely and orderly recruitment of repair factors to damaged sites. After replication stress and double-strand break formation a number of repair factors are Sumoylated and interact with other Sumoylated factors, including the nuclease Yen1. Yen1 plays a critical role to ensure genome stability and unperturbed chromosome segregation by removing covalently linked DNA intermediates that are formed by homologous recombination. Here we show how this important role of Yen1 is dependent on interactions mediated by non-covalent binding to Sumoylated partners. Mutations in the motifs that allow Sumo-mediated recruitment of Yen1 impair its ability to resolve DNA intermediates and result in increased genome instability and chromosome mis-segregation.