Rif1 regulates telomere length through conserved HEAT repeats

@article{Shubin2020Rif1RT,
  title={Rif1 regulates telomere length through conserved HEAT repeats},
  author={Calla B. Shubin and Rini Mayangsari and Ariel D. Swett and Carol W. Greider},
  journal={Nucleic Acids Research},
  year={2020},
  volume={49},
  pages={3967 - 3980}
}
In budding yeast, Rif1 negatively regulates telomere length, but the mechanism of this regulation has remained elusive. Previous work identified several functional domains of Rif1, but none of these has been shown to mediate telomere length. To define Rif1 domains responsible for telomere regulation, we localized truncations of Rif1 to a single specific telomere and measured telomere length of that telomere compared to bulk telomeres. We found that a domain in the N-terminus containing HEAT… 
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References

SHOWING 1-10 OF 47 REFERENCES
Counting of Rif1p and Rif2p on Saccharomyces cerevisiae Telomeres Regulates Telomere Length
TLDR
It is proposed that a nucleation and spreading mechanism is involved in forming the higher-order telomeres structure that regulates telomere length, and Rap1p counting is in fact Rif protein counting.
Functional diversification of yeast telomere associated protein, Rif1, in higher eukaryotes
TLDR
Telomeres are maintained by retrotransposons in all Drosophila species and consequently, telomerase and many of the telomere associated protein homologues are absent, including Rap1, which is the binding partner of Rif1.
The Role of Rif1 in telomere length regulation is separable from its role in origin firing
TLDR
It is concluded that telomeric origin firing does not cause telomere elongation, and the role of Rif1 in regulating origin firing is separable from its role in regulating telomeres length.
Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends
TLDR
Crystal structures for the uncharacterized and conserved ∼125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD) are described, revealing an α-helical fold shaped like a shepherd's crook that fully encases DNA as a head-to-tail dimer in DNA repair.
A Protein-Counting Mechanism for Telomere Length Regulation in Yeast
In the yeast Saccharomyces cerevisiae, telomere elongation is negatively regulated by the telomere repeat-binding protein Rap1p, such that a narrow length distribution of telomere repeat tracts is
Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules
TLDR
A novel subcellular localization behavior for hRif1 during the cell cycle is defined, which efficiently translocated to telomerically located DNA damage foci in response to the synthesis of aberrant telomeres directed by mutant-template telomerase RNA.
At Short Telomeres Tel1 Directs Early Replication and Phosphorylates Rif1
TLDR
Overall, the results reveal two new functions of Tel1 at shortened telomeres: phosphorylation of Rif1, and specification of early replication by counteracting the RIF1-mediated delay in initiation at nearby replication origins.
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