Beyond interacting with Rap1: Dissecting the roles of Rif1

Rap1 interacting factor 1 (Rif1), an evolutionarily conserved protein discovered in budding yeast, is crucial for controlling telomere length when it interacts with Rap1. Recent research, however, has shown that Rif1 not only controls telomere length and homeostasis, but also plays a role in transcriptional silencing, DNA replication timing, DNA replication fork protection, DNA damage repair and chromatin architecture. In this review, we summarize the current understanding of Rif1 in structure, function, and regulation, especially its relevance to cancer hallmarks. Also, we discuss its role as a regulator in the pathogenesis of disease.