An Anti-Checkpoint Activity for Rif1

Harari, Yaniv; Rubinstein, Linda; Kupiec, Martin

doi:10.1371/journal.pgen.1002421

Cited by 5 publications

(4 citation statements)

References 12 publications

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“…As with the above described Rap1 ChIP, we confirmed that Rap1 protein levels were not altered in rif1Δ and rif2Δ cells which may have accounted for observed differences ( Figure S3A ). From here on we have performed further analysis only with the rif2Δ mutant rather that rif1Δ cells due to the fact that apart from telomere length regulation, Rif1 also plays an important role in telomere capping [10] , checkpoint regulation [34] – [35] as well as telomere localization [36] , which greatly complicated the interpretation of rif1Δ cells and their genetic interactions. Ongoing studies are directed at better understand the contributions of Rif1 in promoting the telomere fold-back structure.…”

Section: Resultsmentioning

confidence: 99%

Rif2 Promotes a Telomere Fold-Back Structure through Rpd3L Recruitment in Budding Yeast

et al. 2012

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Using a genome-wide screening approach, we have established the genetic requirements for proper telomere structure in Saccharomyces cerevisiae. We uncovered 112 genes, many of which have not previously been implicated in telomere function, that are required to form a fold-back structure at chromosome ends. Among other biological processes, lysine deacetylation, through the Rpd3L, Rpd3S, and Hda1 complexes, emerged as being a critical regulator of telomere structure. The telomeric-bound protein, Rif2, was also found to promote a telomere fold-back through the recruitment of Rpd3L to telomeres. In the absence of Rpd3 function, telomeres have an increased susceptibility to nucleolytic degradation, telomere loss, and the initiation of premature senescence, suggesting that an Rpd3-mediated structure may have protective functions. Together these data reveal that multiple genetic pathways may directly or indirectly impinge on telomere structure, thus broadening the potential targets available to manipulate telomere function.

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Section: Resultsmentioning

confidence: 99%

Rif2 Promotes a Telomere Fold-Back Structure through Rpd3L Recruitment in Budding Yeast

et al. 2012

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“…Rif1 seems to play an independent role in transducing environmental signals to the telomere‐maintaining machinery (Harari et al ., ; Romano et al ., ), a role not shared with Rif2. Surprisingly, Rif1 seems also to carry out checkpoint‐regulating functions at the telomeres independently of Rap1 (Feldheim et al ., ; Harari et al ., ; Xue et al ., ; Escribano‐Diaz et al ., ; Zimmermann et al ., ). This finding suggests that Rif1 may be able to bind DNA sequences by itself.…”

Section: Telomeric Proteinsmentioning

confidence: 99%

Biology of telomeres: lessons from budding yeast

Kupiec

2014

FEMS Microbiol Rev

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Telomeres are nucleoprotein structures that cap the ends of the linear eukaryotic chromosomes and thereby protect their stability and integrity. Telomeres play central roles in maintaining the genome's integrity, distinguishing between the natural chromosomal ends and unwanted double-stranded breaks. In addition, telomeres are replicated by a special reverse transcriptase called telomerase, in a complex mechanism that is coordinated with the genome's replication. Telomeres also play an important role in tethering the chromosomes to the nuclear envelope, thus helping in positioning the chromosomes within the nucleus. The special chromatin configuration of telomeres affects the expression of nearby genes; nonetheless, telomeres are transcribed, creating noncoding RNA molecules that hybridize to the chromosomal ends and seem to play regulatory roles. The yeast Saccharomyces cerevisiae, with its sophisticated genetics and molecular biology, has provided many fundamental concepts in telomere biology, which were later found to be conserved in all organisms. Here, we present an overview of all the aspects of telomere biology investigated in yeast, which continues to provide new insights into this complex and important subject, which has significant medical implications, especially in the fields of aging and cancer.

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“…As such, we identified a putative cruciform DNA recognition protein (Pa_2_440), an ATPase involved in DNA repair (Pa_6_4260), a SIK1-like RNA-binding protein (Pa_5_12950) and the telomere length regulator protein Rif1 (Pa_1_3890). In mammals as in yeast, Rif1 is required for checkpoint-mediated cell cycle arrest in response to DNA damage [63].…”

Section: Resultsmentioning

confidence: 99%

A RID-like putative cytosine methyltransferase homologue controls sexual development in the fungus Podospora anserina

et al. 2019

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DNA methyltransferases are ubiquitous enzymes conserved in bacteria, plants and opisthokonta. These enzymes, which methylate cytosines, are involved in numerous biological processes, notably development. In mammals and higher plants, methylation patterns established and maintained by the cytosine DNA methyltransferases (DMTs) are essential to zygotic development. In fungi, some members of an extensively conserved fungal-specific DNA methyltransferase class are both mediators of the Repeat Induced Point mutation (RIP) genome defense system and key players of sexual reproduction. Yet, no DNA methyltransferase activity of these purified RID (RIP deficient) proteins could be detected in vitro . These observations led us to explore how RID-like DNA methyltransferase encoding genes would play a role during sexual development of fungi showing very little genomic DNA methylation, if any. To do so, we used the model ascomycete fungus Podospora anserina . We identified the PaRid gene, encoding a RID-like DNA methyltransferase and constructed knocked-out Δ PaRid defective mutants. Crosses involving P . anserina Δ PaRid mutants are sterile. Our results show that, although gametes are readily formed and fertilization occurs in a Δ PaRid background, sexual development is blocked just before the individualization of the dikaryotic cells leading to meiocytes. Complementation of Δ PaRid mutants with ectopic alleles of PaRid , including GFP-tagged, point-mutated and chimeric alleles, demonstrated that the catalytic motif of the putative PaRid methyltransferase is essential to ensure proper sexual development and that the expression of PaRid is spatially and temporally restricted. A transcriptomic analysis performed on mutant crosses revealed an overlap of the PaRid-controlled genetic network with the well-known mating-types gene developmental pathway common to an important group of fungi, the Pezizomycotina.

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An Anti-Checkpoint Activity for Rif1

Cited by 5 publications

References 12 publications

Rif2 Promotes a Telomere Fold-Back Structure through Rpd3L Recruitment in Budding Yeast

Rif2 Promotes a Telomere Fold-Back Structure through Rpd3L Recruitment in Budding Yeast

Biology of telomeres: lessons from budding yeast

A RID-like putative cytosine methyltransferase homologue controls sexual development in the fungus Podospora anserina

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