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

Rif1 Regulates the Fate of DNA Entanglements during Mitosis.

Author information

1
Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
2
Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: julie.cooper@nih.gov.

Abstract

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

PMID:
27320927
PMCID:
PMC4929174
DOI:
10.1016/j.celrep.2016.05.077
[Indexed for MEDLINE]
Free PMC Article

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