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Peer-reviewedCC BY-NC-NDCell Reports

Rif1 Controls DNA Replication Timing in Yeast through the PP1 Phosphatase Glc7

Abstract

The Rif1 protein, originally identified as a telomere-binding factor in yeast, has recently been implicated in DNA replication control from yeast to metazoans. Here, we show that budding yeast Rif1 protein inhibits activation of prereplication complexes (pre-RCs). This inhibitory function requires two N-terminal motifs, RVxF and SILK, associated with recruitment of PP1 phosphatase (Glc7). In G1 phase, we show both that Glc7 interacts with Rif1 in an RVxF/SILK-dependent manner and that two proteins implicated in pre-RC activation, Mcm4 and Sld3, display increased Dbf4-dependent kinase (DDK) phosphorylation in rif1 mutants. Rif1 also interacts with Dbf4 in yeast two-hybrid assays, further implicating this protein in direct modulation of pre-RC activation through the DDK. Finally, we demonstrate Rif1 RVxF/SILK motif-dependent recruitment of Glc7 to telomeres and earlier replication of these regions in cells where the motifs are mutated. Our data thus link Rif1 to negative regulation of replication origin firing through recruitment of the Glc7 phosphatase.

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BibTeX
@article{mattarocci2026rif1,
  title = {{Rif1 Controls DNA Replication Timing in Yeast through the PP1 Phosphatase Glc7}},
  author = {Stefano Mattarocci and Maksym Shyian and Laure Lemmens and Pascal Damay and Dogus Murat Altintas and Tianlai Shi and Clinton R. Bartholomew and Nicolas Thomä and Christopher F.J. Hardy and David Shore},
  journal = {Cell Reports},
  year = {2026},
  month = sep,
  doi = {10.1016/j.celrep.2014.03.010},
  url = {https://hal.science/hal-05771427v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Rif1 Controls DNA Replication Timing in Yeast through the PP1 Phosphatase Glc7
AU  - Stefano Mattarocci
AU  - Maksym Shyian
AU  - Laure Lemmens
AU  - Pascal Damay
AU  - Dogus Murat Altintas
AU  - Tianlai Shi
AU  - Clinton R. Bartholomew
AU  - Nicolas Thomä
AU  - Christopher F.J. Hardy
AU  - David Shore
PY  - 2026
DA  - 2026/09/30
JO  - Cell Reports
DO  - 10.1016/j.celrep.2014.03.010
UR  - https://hal.science/hal-05771427v1
AB  - The Rif1 protein, originally identified as a telomere-binding factor in yeast, has recently been implicated in DNA replication control from yeast to metazoans. Here, we show that budding yeast Rif1 protein inhibits activation of prereplication complexes (pre-RCs). This inhibitory function requires two N-terminal motifs, RVxF and SILK, associated with recruitment of PP1 phosphatase (Glc7). In G1 phase, we show both that Glc7 interacts with Rif1 in an RVxF/SILK-dependent manner and that two proteins implicated in pre-RC activation, Mcm4 and Sld3, display increased Dbf4-dependent kinase (DDK) phosphorylation in rif1 mutants. Rif1 also interacts with Dbf4 in yeast two-hybrid assays, further implicating this protein in direct modulation of pre-RC activation through the DDK. Finally, we demonstrate Rif1 RVxF/SILK motif-dependent recruitment of Glc7 to telomeres and earlier replication of these regions in cells where the motifs are mutated. Our data thus link Rif1 to negative regulation of replication origin firing through recruitment of the Glc7 phosphatase.
SN  - 2211-1247
SN  - 2211-1247
ER  -