Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends

@article{Mattarocci2017Rif1MT,
  title={Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends},
  author={Stefano Mattarocci and Julia K Reinert and Richard D. Bunker and Gabriele A Fontana and Tianlai Shi and Dominique Klein and Simone Cavadini and Mahamadou Faty and Maksym Shyian and Lukas Hafner and David Shore and Nicolas H. Thom{\"a} and Ulrich Rass},
  journal={Nature Structural \&Molecular Biology},
  year={2017},
  volume={24},
  pages={588-595}
}
In yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved ∼125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an α-helical fold shaped like a shepherd's crook. We identify a… 
Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks
TLDR
An overview of the actions of RIF1 at DNA ends is provided and how exclusion of end-processing factors might be the underlying principle allowing Rif1 to fulfill diverse biological roles at telomeres and chromosome breaks is explored.
Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane
TLDR
Rif1 S-acylation facilitates the accumulation of Rif1 at DSBs, attenuation of DNA end-resection, and DSB repair by non-homologous end-joining by the DHHC family palmitoyl acyltransferase Pfa4.
Budding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks
Despite its evolutionarily conserved function in controlling DNA replication, the chromosomal binding sites of the budding yeast Rif1 protein are not well understood. Here, we analyse genome‐wide
Oligomer formation and G-quadruplex binding by purified murine Rif1 protein, a key organizer of higher-order chromatin architecture
TLDR
Hydrodynamic analyses indicated that Rif1 forms elongated or extended homo-oligomers in solution, consistent with the presence of a HEAT-type helical repeat segment known to adopt an elongated shape, and pulldown assays revealed that R if1 simultaneously binds multiple G4 molecules.
The effect of telomeric repeats on double-strand break processing and repair
TLDR
Nearly all survivors of repeat-proximal DSBs repair the break by a homology-driven, non-reciprocal translocation from ChrIII-R to ChrVII-L, and suppression of imprecise NHEJ at TG-repeat-flanked D SBs requires the Uls1 translocase activity.
Rif1 acts through Protein Phosphatase 1 but independent of replication timing to suppress telomere extension in budding yeast
TLDR
The results show that Rif1 controls telomere length by recruiting PP1 to directly suppress telomerase-mediated TG repeat lengthening and prevent inappropriate recruitment of Tel1 kinase.
Rif1 regulates telomere length through conserved HEAT repeats
TLDR
It is proposed that the Rif1 HEAT repeats region represents a protein-protein binding interface that mediates telomere length regulation, which is separate from their proposed DNA-binding function.
Drosophila Rif1 is critical for repair following P-element excision and influences pathway choice at double-strand breaks
TLDR
The role of Rif1 in double-strand break repair in Drosophila melanogaster is explored and it is found that rif1 mutants are not sensitive to ionizing radiation or hydroxyurea, demonstrating that it is not essential for the resolution of DNA damage in Dosophila.
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References

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TLDR
The deployment of Rif1 at telomeres in yeasts is discussed from both an evolutionary perspective and in light of its recently discovered global functions.
Rif1 Supports the Function of the CST Complex in Yeast Telomere Capping
TLDR
A novel role for Rif1 is highlighted in assisting the essential telomere protection function of the CST complex, because RIF1 deletion does not enhance checkpoint activation in case of CST-independent telomeres capping deficiencies, such as those caused by the absence of Yku or telomerase.
Anticheckpoint pathways at telomeres in yeast
TLDR
The response in Saccharomyces cerevisiae to DNA double-strand breaks flanked by varying amounts of telomeric repeat sequences (TG1–3) is characterized and it is shown that even short arrays of TG1-3 repeats do not induce G2/M arrest.
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.
Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint.
TLDR
The data reveal that human Rif1 contributes to the ATM-mediated protection against DNA damage and point to a remarkable difference in the primary function of this protein in yeast and mammals.
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TLDR
Using dysfunctional telomeres and genome-wide DSBs, Rif1 is identified as the main factor used by 53BP1 to impair 5′ end resection and established as an important contributor to the control of DSB repair by 53 BP1.
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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.
Rif1 Prevents Resection of DNA Breaks and Promotes Immunoglobulin Class Switching
TLDR
Rap1-interacting factor 1 (Rif1) is identified as an ATM (ataxia-telangiectasia mutated) phosphorylation-dependent interactor of 53BP1 and it is shown that absence of Rif1 results in 5′-3′ DNA-end resection in mice.
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