R.I.P. to the PIP: PCNA‐binding motif no longer considered specific

Many proteins responsible for genome maintenance interact with one another via short sequence motifs. The best known of these are PIP motifs, which mediate interactions with the replication protein PCNA. Others include RIR motifs, which bind the translesion synthesis protein Rev1, and MIP motifs, which bind the mismatch repair protein Mlh1. Although these motifs have similar consensus sequences, they have traditionally been viewed as separate motifs, each with their own target protein. In this article, we review several recent studies that challenge this view. Taken together, they imply that these different motifs are not distinct entities. Instead, there is a single, broader class of motifs, which we call "PIP-like" motifs, which have overlapping specificities and are capable of binding multiple target proteins. Given this, we must reassess the role of these motifs in forming the network of interacting proteins responsible for genome maintenance.