Involvement of TOPBP1 in HR-mediated repair. (A) The work by Moudry et al. (2016) supports a model in which TOPBP1 directs the action of PLK1 kinase toward RAD51, mediating a phosphorylation event that licenses a second phosphorylation event mediated by the casein kinase 2 (CK2) kinase. These phosphorylation events are believed to facilitate the loading of RAD51, which replaces RPA, at damage sites and favor HR. (B) TOPBP1 as a hub for coordinating the action of multiple kinases toward genome maintenance. (C) Speculative model for the mutually exclusive engagement of TOPBP1 in distinct cellular processes as a strategy for coordinating genome replication and DNA damage responses (see text for details). (D) Current understanding of how TOPBP1 and its yeast orthologue Dpb11 mediate the formation of ternary complexes for replication initiation, DNA damage signaling, and recombinational repair. In mammals, the indicated proteins have been shown to interact with TOPBP1, but the roles of most of those interactions remain unclear. For simplicity, some TOPBP1 interactions and their cofactors are not depicted.