“…In eukaryotes, PI3K-like kinases (PIKKs) play essential roles in the sensing of DNA damage and the coordination of cell cycle checkpoint activation and DNA repair mechanisms to maintain genome stability (Savitsky et al, 1995; Shiloh, 2003). In Saccharomyces cerevisiae , the Mec1 PIKK (human ATR) plays a central role in coordinating the response to DNA lesions that result in single stranded DNA (ssDNA) exposure, including stalled replication forks and recessed double strand breaks (DSBs) (Cha & Kleckner, 2002; Deshpande et al, 2017; Segurado & Diffley, 2008; Tercero, Longhese, & Diffley, 2003). Mec1 senses ssDNA exposure through the recognition of replication protein A (RPA)-bound ssDNA via its obligate cofactor Ddc2 (human ATRIP) (Deshpande et al, 2017; Paciotti, Clerici, Lucchini, & Longhese, 2000; Zou & Elledge, 2003).…”