Replication Timing Regulatory Factor 1 (RIF1)

RIF1 contains 2,472 amino acids. Alignment of the human, mouse, and fugu proteins revealed 2 conserved N-terminal regions and a conserved C-terminal region. The first 340 amino acids contain 8 armadillo-type repeats, which are helical folds that typically occur in long arrays, creating an extended curved protein or RNA interaction surface. RIF1 also contains a central serine-rich region and a bipartite nuclear localization signal within the C-terminal conserved region.After induction of double-strand breaks in ALT cells, RIF1 formed foci that colocalized with other DNA damage response factors. This response was strictly dependent on ATM and 53BP1, but was not affected by diminished function of ATR, BRCA1, CHK2, NBS1, or MRE11. RIF1 inhibition resulted in radiosensitivity and a defect in the intra-S-phase checkpoint.