Rif1: A Conserved Regulator of DNA Replication and Repair Hijacked by Telomeres in Yeasts

@article{Mattarocci2016Rif1AC,
  title={Rif1: A Conserved Regulator of DNA Replication and Repair Hijacked by Telomeres in Yeasts},
  author={Stefano Mattarocci and Lukas Hafner and Aleksandra Lezaja and Maksym Shyian and David Shore},
  journal={Frontiers in Genetics},
  year={2016},
  volume={7}
}
Rap1-interacting factor 1 (Rif1) was originally identified in the budding yeast Saccharomyces cerevisiae as a telomere-binding protein that negatively regulates telomerase-mediated telomere elongation. Although this function is conserved in the distantly related fission yeast Schizosaccharomyces pombe, recent studies, both in yeasts and in metazoans, reveal that Rif1 also functions more globally, both in the temporal control of DNA replication and in DNA repair. Rif1 proteins are large and… 

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TLDR
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Establishment of expression-state boundaries by Rif1 and Taz1 in fission yeast
TLDR
High-throughput genetic screens designed to identify cis- and trans-acting factors capable of creating heterochromatin–euchromatin boundaries in fission yeast identified unexpected properties for Rif1 and Taz1, providing an insight into a coordinated control of DNA replication and organization of the genome into expression domains.
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References

SHOWING 1-10 OF 76 REFERENCES
Rif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7.
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.
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.
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.
A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae.
TLDR
The results suggest that telomere length regulation is mediated by a protein complex consisting of Rif1p and Rif2p, each of which has distinct regulatory functions.
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.
Rif1 is a global regulator of timing of replication origin firing in fission yeast.
TLDR
The data demonstrate that Rif1 is a critical determinant of the origin activation program on the fission yeast chromosomes.
Rif1 provides a new DNA‐binding interface for the Bloom syndrome complex to maintain normal replication
TLDR
V vertebrate Rif1 contains a DNA‐binding domain that resembles the αCTD domain of bacterial RNA polymerase α; and this domain preferentially binds fork and Holliday junction (HJ) DNA in vitro and is required for R if1 to resist replication stress in vivo.
A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation.
TLDR
The two-hybrid system is used to suggest that RIF1 is a cofactor or mediator for RAP1 in the establishment of a repressed chromatin state at these loci and support the idea that the rap1s phenotypes are attributable to a failure to recruit Rif1 to silencers and telomeres.
...
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