Exo1 cooperates with Tel1/ATM in promoting recombination events at DNA replication forks

: Tel1/ataxia telangiectasia mutated (ATM) kinase plays multiple functions in response to DNA damage, promoting checkpoint-mediated cell-cycle arrest and repair of broken DNA. In addition, Saccharomyces cerevisiae Tel1 stabilizes replication forks that arrest upon the treatment with the topoisomerase poison camptothecin (CPT). We discover that inactivation of the Exo1 nuclease exacerbates the sensitivity of Tel1-deficient cells to CPT and other agents that hamper DNA replication. Furthermore, cells lacking both Exo1 and Tel1 activities exhibit sustained checkpoint activation in the presence of CPT, indicating that Tel1 and Exo1 limit the activation of a Mec1-dependent checkpoint. The absence of Tel1 or its kinase activity enhances recombination between inverted DNA repeats induced by replication fork blockage in an Exo1-dependent manner. Thus, we propose that Exo1 processes intermediates arising at stalled forks in tel1 mutants to promote DNA replication recovery and cell survival.