Figure 7. Possible Substrates onto Which the Checkpoint Clamp Loader RSR May Load Its Clamp (RHR).

DNA maintenance pathways, including those depicted here, generate intermediates containing free and/or recessed 3′ ends that are processed by a variety of proteins. These structures also contain recessed 5′ ends, whose fate in these reactions is unclear. Given that RSR loads RHR (depicted as a ring or donut encircling the DNA) onto recessed 5′ ends in vitro, recessed 5′ ends generated in vivo in the depicted pathways can be considered potential substrates. They all contain adjacent single-stranded DNA that could be bound by RPA. RHR has been shown to be required for checkpoint signaling in response to DNA replication fork arrest (Longhese et al. 1997), double-strand breaks (Kondo et al. 2001; Melo et al. 2001), and improper telomere maintenance (Garvik et al. 1995; Lydall and Weinert 1995; Longhese et al. 2000). The RHR clamp is proposed to protect the recessed 5′ end from extensive degradation by exonucleases and to promote resolution of these structures back to duplex DNA.