<i>Saccharomyces</i> Rrm3p, a 5′ to 3′ DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA

Ivessa, Andreas S.; Zhou, Juanjuan; Schulz, Vincent P.; Monson, Ellen K.; Zakian, Virginia A.

doi:10.1101/gad.982902

Cited by 260 publications

(359 citation statements)

References 49 publications

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“…3). This characteristic DNA replication profile has been demonstrated previously for rrm3 mutants, and is proposed to be a consequence of increased origin usage, coupled with genome-wide RF stalling at 41,000 predicted sites in rrm3 mutants 10,[27][28][29] . We also observed that two tandem arrays of 3xTer modules (when the origin-distal array was arranged in either the permissive or restrictive orientation) behaved similarly in both wild-type and rrm3 strains ( Supplementary Fig.…”

Section: Tus-ter Modules Cause Polar Rf Pausing In Yeast the 21-bpmentioning

confidence: 79%

The Escherichia coli Tus–Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

et al. 2014

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Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus, to specific DNA sequences called Ter. Here, we demonstrate that Tus-Ter modules also induce polar RF pausing when engineered into the Saccharomyces cerevisiae genome. This heterologous RF barrier is distinct from a number of previously characterized, protein-mediated, RF pause sites in yeast, as it is neither Tof1-dependent nor counteracted by the Rrm3 helicase. Although the yeast replisome can overcome RF pausing at Tus-Ter modules, this event triggers site-specific homologous recombination that requires the RecQ helicase, Sgs1, for its timely resolution. We propose that Tus-Ter can be utilized as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications.

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Section: Tus-ter Modules Cause Polar Rf Pausing In Yeast the 21-bpmentioning

confidence: 79%

The Escherichia coli Tus–Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

et al. 2014

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“…Since deletion of ScPIF1 leads to an increase in mitochondrial DNA point mutations, particularly after oxidative damage (21,51,52,67), it is also possible mPif1 plays a nonessential role in mitochondrial genome stability. Although Scrrm3⌬ cells do not exhibit changes in GCR or mitochondrial genome stability, these cells do exhibit genetic instability, presumably due to replication fork pausing at specific chromosomal loci, such as the ribosomal DNA locus (31,32,45,59,68,69). ScRRM3 and ScPIF1 exhibit genetic interactions (including synthetic lethality) with many gene products required in DNA replication and S-phase checkpoint arrest (1,2,17,50,58,59,69,71).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike Rrm3 and Pif1, Pfh1 is essential (77). Rrm3 promotes the progression of replication forks at particular chromosomal loci prone to pausing during DNA replication (including the telomere), and rrm3⌬ cells exhibit a modest telomere lengthening (11,32,33,45,59,69). Mutation of ScPif1 leads to telomerase-dependent telomere lengthening (33,76), and this phenotype depends on the ATPunwinding activity of ScPif1; the enzyme has a preference for short (Ͻ30 nucleotides) RNA-DNA hybrids and can unwind telomerase RNA from a telomeric DNA substrate (15).…”

mentioning

confidence: 99%

Murine Pif1 Interacts with Telomerase and Is Dispensable for Telomere Function In Vivo

Snow

Mateyak

Paderova

et al. 2007

Molecular and Cellular Biology

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Pif1 is a 5 -to-3 DNA helicase critical to DNA replication and telomere length maintenance in the budding yeast Saccharomyces cerevisiae. ScPif1 is a negative regulator of telomeric repeat synthesis by telomerase, and recombinant ScPif1 promotes the dissociation of the telomerase RNA template from telomeric DNA in vitro. In order to dissect the role of mPif1 in mammals, we cloned and disrupted the mPif1 gene. In wild-type animals, mPif1 expression was detected only in embryonic and hematopoietic lineages. mPif1 ؊/؊ mice were viable at expected frequencies, displayed no visible abnormalities, and showed no reproducible alteration in telomere length in two different null backgrounds, even after several generations. Spectral karyotyping of mPif1 ؊/؊ fibroblasts and splenocytes revealed no significant change in chromosomal rearrangements. Furthermore, induction of apoptosis or DNA damage revealed no differences in cell viability compared to what was found for wild-type fibroblasts and splenocytes. Despite a novel association of mPif1 with telomerase, mPif1 did not affect the elongation activity of telomerase in vitro. Thus, in contrast to what occurs with ScPif1, murine telomere homeostasis or genetic stability does not depend on mPif1, perhaps due to fundamental differences in the regulation of telomerase and/or telomere length between mice and yeast or due to genetic redundancy with other DNA helicases.Homeostatic telomere length is achieved by a balance between the extension of the 3Ј telomeric repeats by telomerase or by homologous recombination between telomeric tracts and telomere erosion due to incomplete DNA replication or nucleolytic degradation (30). Telomerase acts to lengthen telomeres via the reverse transcription of an RNA template (encoded by TERC in mammals or TLC1 in Saccharomyces cerevisiae) by a telomerase reverse transcriptase (TERT or Est2, respectively) (30). In the absence of telomerase, telomeric repeats can also be maintained via homologous recombination (12). Excessive telomere lengthening is usually curtailed by cis-inhibitory telomere binding factors, such as Rif1 and Rap1 in S. cerevisiae and TRF1 in humans, or by the action of nucleases (30). In particular instances, telomeric tracts undergo saltatory attrition via the excision of telomeric DNA circles, thus preventing unregulated telomere lengthening (12,40,73).This equilibrium is not simply a push and pull between factors that strictly promote or oppose telomere extension. In S. cerevisiae, the trimeric protein complex composed of Cdc13, Stn1, and Ten1 plays a critical role in the protection of chromosome ends from nucleolytic degradation, and the complex serves both positive and negative roles in the access of telomerase to the telomere during late S phase (24,27,66). The Ku70/Ku80 heterodimer, while essential for nonhomologous end joining, also plays a key role both in the recruitment of telomerase to the telomere and in the protection of ends from degradation (9,25,65,74). Several DNA helicases and nucleases are also known to play ...

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“…Only in recent years did it become apparent that even the semiconservative replication of telomeric DNA is difficult, requiring specialized helicases and telomerebinding proteins. In S. cerevisiae, the Rrm3 5 0 -3 0 helicase prevents replication fork stalling at telomeres (Ivessa et al 2002;Makovets et al 2004). In fission yeast, it was noted that efficient replication of telomeric DNA requires the telomere-binding protein Taz1 (Miller et al 2006).…”

Section: Telomerasementioning

confidence: 99%

Replication of Telomeres and the Regulation of Telomerase

Pfeiffer

Lingner

2013

Cold Spring Harbor Perspectives in Biology

110

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Telomeres are the physical ends of eukaryotic chromosomes. They protect chromosome ends from DNA degradation, recombination, and DNA end fusions, and they are important for nuclear architecture. Telomeres provide a mechanism for their replication by semiconservative DNA replication and length maintenance by telomerase. Through telomerase repression and induced telomere shortening, telomeres provide the means to regulate cellular life span. In this review, we introduce the current knowledge on telomere composition and structure. We then discuss in depth the current understanding of how telomere components mediate their function during semiconservative DNA replication and how telomerase is regulated at the end of the chromosome. We focus our discussion on the telomeres from mammals and the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe.

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Saccharomyces Rrm3p, a 5′ to 3′ DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA

Cited by 260 publications

References 49 publications

The Escherichia coli Tus–Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

The Escherichia coli Tus–Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

Murine Pif1 Interacts with Telomerase and Is Dispensable for Telomere Function In Vivo

Replication of Telomeres and the Regulation of Telomerase

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