Rap1-interacting factor 1 (Rif1) was originally identified in the budding yeast 
Saccharomyces cerevisiae as a telomere-binding protein that negatively regulates 
telomerase-mediated telomere elongation. Although this function is conserved in 
the distantly related fission yeast Schizosaccharomyces pombe, recent studies, 
both in yeasts and in metazoans, reveal that Rif1 also functions more globally, 
both in the temporal control of DNA replication and in DNA repair. Rif1 proteins 
are large and characterized by N-terminal HEAT repeats, predicted to form an 
elongated alpha-helical structure. In addition, all Rif1 homologs contain two 
short motifs, abbreviated RVxF/SILK, that are implicated in recruitment of the 
PP1 (yeast Glc7) phosphatase. In yeasts the RVxF/SILK domains have been shown to 
play a role in control of DNA replication initiation, at least in part through 
targeted de-phosphorylation of proteins in the pre-Replication Complex. In human 
cells Rif1 is recruited to DNA double-strand breaks through an interaction with 
53BP1 where it counteracts DNA resection, thus promoting repair by 
non-homologous end-joining. This function requires the N-terminal HEAT 
repeat-containing domain. Interestingly, this domain is also implicated in DNA 
end protection at un-capped telomeres in yeast. We conclude by discussing the 
deployment of Rif1 at telomeres in yeasts from both an evolutionary perspective 
and in light of its recently discovered global functions.