Rif1 Regulates the Fate of DNA Entanglements during Mitosis.
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.
Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Sophie
S
Zaaijer
Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Nadeem
N
Shaikh
Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Rishi Kumar
RK
Nageshan
Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: julie.cooper@nih.gov.
Julia Promisel
JP
Cooper
D000705:Anaphase; D059447:Cell Cycle Checkpoints; D002503:Centromere / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism; D004261:DNA Replication; D004271:DNA, Fungal / Q000737:chemistry* / Q000378:metabolism*; D004275:DNA, Ribosomal / Q000378:metabolism; D008938:Mitosis; D051716:Replication Protein A / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000378:metabolism*
D004271:DNA, Fungal; D004275:DNA, Ribosomal; D051716:Replication Protein A; C570600:Rif1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D034501:Telomere-Binding Proteins
Rif1; Taz1; anaphase; chromosome segregation; phosphatase; replication fork stalling; telomere; ultrafine anaphase bridge