Rif1 Regulates the Fate of DNA Entanglements during Mitosis

Cell Rep. 2016 Jun 28;16(1):148-160. doi: 10.1016/j.celrep.2016.05.077. Epub 2016 Jun 16.


Clearance of entangled DNA from the anaphase mid-region must accurately proceed in order for chromosomes to segregate with high fidelity. Loss of Taz1 (fission yeast ortholog of human TRF1/TRF2) leads to stalled telomeric replication forks that trigger telomeric entanglements; the resolution of these entanglements fails at ≤20°C. Here, we investigate these entanglements and their promotion by the conserved replication/repair protein Rif1. Rif1 plays no role in taz1Δ fork stalling. Rather, Rif1 localizes to the anaphase mid-region and regulates the resolution of persisting DNA structures. This anaphase role for Rif1 is genetically separate from the role of Rif1 in S/G2, though both roles require binding to PP1 phosphatase, implying spatially and temporally distinct Rif1-regulated phosphatase substrates. Rif1 thus acts as a double-edged sword. Although it inhibits the resolution of taz1Δ telomere entanglements, it promotes the resolution of non-telomeric ultrafine anaphase bridges at ≤20°C. We suggest a unifying model for Rif1's seemingly diverse roles in chromosome segregation in eukaryotes.

Keywords: Rif1; Taz1; anaphase; chromosome segregation; phosphatase; replication fork stalling; telomere; ultrafine anaphase bridge.

MeSH terms

  • Anaphase
  • Cell Cycle Checkpoints
  • Centromere / metabolism
  • Chromatids / metabolism
  • DNA Replication
  • DNA, Fungal / chemistry*
  • DNA, Fungal / metabolism*
  • DNA, Ribosomal / metabolism
  • Mitosis*
  • Replication Protein A / metabolism
  • Schizosaccharomyces / cytology*
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Telomere / metabolism
  • Telomere-Binding Proteins / metabolism*


  • DNA, Fungal
  • DNA, Ribosomal
  • Replication Protein A
  • Rif1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Telomere-Binding Proteins