Multiple regulatory roles of Rad9 C-tail in DNA damage responses

Abstract

DNA damage response (DDR) pathways play crucial roles in the maintenance of genome integrity, and defects in DDR proteins lead to genome instability and eventually cancer. Rad9-Hus1-Rad1 (9-1-1) is a ring-shaped heterotrimeric complex involved in multiple DDR pathways, especially the DNA damage checkpoint. Rad9 has an intrinsically disordered C-terminal region, called C-tail. The C-tail projects from the ring and has multiple phosphorylation sites and several protein-protein interaction sites, some of which are crucial for checkpoint activation. In addition, it was recently shown that C-tail binds to the 9-1-1 ring structure and is released from it upon binding to TopBP1, an activator of the DNA damage checkpoint. This review focuses on the regulatory roles of the Rad9 C-tail and discusses DNA damage checkpoint activation and the regulation of several DNA repair pathways via this region.