Evidence that the S.cerevisiae Sgs1 protein facilitates recombinational repair of telomeres during senescence

Azam, Mahrukh; Lee, Julia Y.; Abraham, Veena; Chanoux, Rebecca A.; Schoenly, Kimberly A.; Johnson, F. Brad

doi:10.1093/nar/gkj452

Cited by 62 publications

(77 citation statements)

References 98 publications

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“…Consistent with this idea, studies in human cells have shown that the absence of the WRN DNA helicase, which like its yeast homologue Sgs1p, is particularly adept at unwinding G4-DNA [39,40,42,87], results in loss of the telomere strand that is replicated by lagging strand synthesis [36]. Telomere defects related to replication in sgs1 mutants might have a similar basis [88,89]. Further, the unwinding of telomere quadruplexes during Stylonichia telomere replication [4,5], and the CGG repeat-induced pausing of DNA polymerases in vitro [90,91], are consistent with G4-DNA providing an impediment to replication.…”

Section: G-quadruplexes and Dna Replicationmentioning

confidence: 88%

In vivo veritas: Using yeast to probe the biological functions of G-quadruplexes

et al. 2008

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Certain guanine-rich sequences are capable of forming higher order structures known as Gquadruplexes. Moreover, particular genomic regions in a number of highly divergent organisms are enriched for such sequences, raising the possibility that G-quadruplexes form in vivo and affect cellular processes. While G-quadruplexes have been rigorously studied in vitro, whether these structures actually form in vivo and what their roles might be in the context of the cell have remained largely unanswered questions. Recent studies suggest that G-quadruplexes participate in the regulation of such varied processes as telomere maintenance, transcriptional regulation and ribosome biogenesis. Here we review studies aimed at elucidating the in vivo functions of quadruplex structures, with a particular focus on findings in yeast. In addition, we discuss the utility of yeast model systems in the study of the cellular roles of G-quadruplexes.

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Section: G-quadruplexes and Dna Replicationmentioning

confidence: 88%

In vivo veritas: Using yeast to probe the biological functions of G-quadruplexes

et al. 2008

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“…(C) Precise NHEJ and imprecise NHEJ were performed and analyzed as described in the Materials and Methods on GA-8860 (wild type) and GA-8471 (nup84Δ). yeast mutants that lack functional telomerase (Azam et al 2006). Also, in yeast, eroded telomeres relocate to nuclear pores (V Geli, pers.…”

Section: Discussionmentioning

confidence: 99%

PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL

et al. 2016

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High-resolution imaging shows that persistent DNA damage in budding yeast localizes in distinct perinuclear foci for repair. The signals that trigger DNA double-strand break (DSB) relocation or determine their destination are unknown. We show here that DSB relocation to the nuclear envelope depends on SUMOylation mediated by the E3 ligases Siz2 and Mms21. In G1, a polySUMOylation signal deposited coordinately by Mms21 and Siz2 recruits the SUMO targeted ubiquitin ligase Slx5/Slx8 to persistent breaks. Both Slx5 and Slx8 are necessary for damage relocation to nuclear pores. When targeted to an undamaged locus, however, Slx5 alone can mediate relocation in G1-phase cells, bypassing the requirement for polySUMOylation. In contrast, in S-phase cells, monoSUMOylation mediated by the Rtt107-stabilized SMC5/6-Mms21 E3 complex drives DSBs to the SUN domain protein Mps3 in a manner independent of Slx5. Slx5/Slx8 and binding to pores favor repair by ectopic break-induced replication and imprecise end-joining.

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“…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). Thus, additional inactivation of other DNA helicases involved in DNA replication or repair or proteins essential for the S-phase checkpoint may yet reveal an interesting phenotype in mPif Ϫ/Ϫ animals.…”

Section: Discussionmentioning

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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Evidence that the S.cerevisiae Sgs1 protein facilitates recombinational repair of telomeres during senescence

Cited by 62 publications

References 98 publications

In vivo veritas: Using yeast to probe the biological functions of G-quadruplexes

In vivo veritas: Using yeast to probe the biological functions of G-quadruplexes

PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL

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

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