Taz1 Enforces Cell-Cycle Regulation of Telomere Synthesis

Dehé, Pierre-Marie; Rog, Ofer; Ferreira, Miguel Godinho; Greenwood, Jessica; Cooper, Julia Promisel

doi:10.1016/j.molcel.2012.04.022

Cited by 39 publications

(54 citation statements)

References 67 publications

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“…This effect was rescued by supplementation with an endogenous copy of Taz1, consistent with Taz1 functioning as part of a counting mechanism as described for Rap1 in budding yeast (Marcand et al 1997). A requirement for coating the bulk of telomeric DNA with Taz1 to limit telomere elongation is also supported by the observation that the dramatic telomere elongation seen in rap1Δ cells is partially rescued by overexpression of Taz1 (Dehe et al 2012). Taken together, these results suggest that telomere length homeostasis requires sufficient Taz1 to coat the available repeats in addition to a physical link between the single-stranded overhang and internal telomeric sequences.…”

Section: Why Telomere Length Regulation Is Sensitive To Taz1 Levelssupporting

confidence: 66%

Minishelterins separate telomere length regulation and end protection in fission yeast

et al. 2015

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The conserved shelterin complex is critical for chromosome capping and maintaining telomere length homeostasis. In fission yeast, shelterin is comprised of five proteins. Taz1, Rap1, and Poz1 function as negative regulators of telomere elongation, whereas Pot1 and Tpz1 are critical for end capping and telomerase recruitment. How the five proteins work together to safeguard chromosome ends and promote telomere length homeostasis is a matter of great interest. Using a combination of deletions, fusions, and tethers, we define key elements of shelterin important for telomere length regulation. Surprisingly, deletion of the entire Rap1 and Poz1 proteins does not impair telomere length regulation as long as a static bridge is provided between Taz1 and Tpz1. Cells harboring minishelterin display wild-type telomere length and intact subtelomeric silencing. However, protection against end fusions in G1 is compromised in the absence of Rap1. Our data reveal a remarkable plasticity in shelterin architecture and separate functions in length regulation and end protection.

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Section: Why Telomere Length Regulation Is Sensitive To Taz1 Levelssupporting

confidence: 66%

Minishelterins separate telomere length regulation and end protection in fission yeast

et al. 2015

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“…The highly elongated telomeres in these mutants contain an excess of Taz1 binding sequences, which probably leads to partially Taz1-deficient telomeres as previously suggested [30]. Because Taz1 acts as one of the establishment factors for telomere heterochromatin by recruiting Clr4, a methyltransferase for histone H3-K9, to telomeres [13], the low abundance of Taz1 at subtelomeres possibly causes a deficiency in telomere heterochromatin structure in the mutants with highly elongated telomeres.…”

Section: Discussionsupporting

confidence: 55%

Identification of the Functional Domains of the Telomere Protein Rap1 in Schizosaccharomyces pombe

2012

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The telomere at the end of a linear chromosome plays crucial roles in genome stability. In the fission yeast Schizosaccharomyces pombe, the Rap1 protein, one of the central players at the telomeres, associates with multiple proteins to regulate various telomere functions, such as the maintenance of telomere DNA length, telomere end protection, maintenance of telomere heterochromatin, and telomere clustering in meiosis. The molecular bases of the interactions between Rap1 and its partners, however, remain largely unknown. Here, we describe the identification of the interaction domains of Rap1 with its partners. The Bqt1/Bqt2 complex, which is required for normal meiotic progression, Poz1, which is required for telomere length control, and Taz1, which is required for the recruitment of Rap1 to telomeres, bind to distinct domains in the C-terminal half of Rap1. Intriguingly, analyses of a series of deletion mutants for rap1 + have revealed that the long N-terminal region (1–456 a.a. [amino acids]) of Rap1 (full length: 693 a.a.) is not required for telomere DNA length control, telomere end protection, and telomere gene silencing, whereas the C-terminal region (457–693 a.a.) containing Poz1- and Taz1-binding domains plays important roles in those functions. Furthermore, the Bqt1/Bqt2- and Taz1-binding domains are essential for normal spore formation after meiosis. Our results suggest that the C-terminal half of Rap1 is critical for the primary telomere functions, whereas the N-terminal region containing the BRCT (BRCA1 C-terminus) and Myb domains, which are evolutionally conserved among the Rap1 family proteins, does not play a major role at the telomeres.

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“…Fold enrichment values were calculated based on Δ Ct between ChIP and input using the jk380/jk381 primer pairs of subtelomere [81] and an act1 (actin) gene fragment as background control (Omn228, Omn229 primers, Table 2). The values were expressed as ChIP/input (subtelomere) normalized with ChIP/input (act1 + ) as described [82]. …”

Section: Methodsmentioning

confidence: 99%

SUMO-targeted ubiquitin ligase activity can either suppress or promote genome instability, depending on the nature of the DNA lesion

Nie¹,

Moser²,

Nakamura³

et al. 2017

PLoS Genet

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The posttranslational modifiers SUMO and ubiquitin critically regulate the DNA damage response (DDR). Important crosstalk between these modifiers at DNA lesions is mediated by the SUMO-targeted ubiquitin ligase (STUbL), which ubiquitinates SUMO chains to generate SUMO-ubiquitin hybrids. These SUMO-ubiquitin hybrids attract DDR proteins able to bind both modifiers, and/or are degraded at the proteasome. Despite these insights, specific roles for SUMO chains and STUbL in the DDR remain poorly defined. Notably, fission yeast defective in SUMO chain formation exhibit near wild-type resistance to genotoxins and moreover, have a greatly reduced dependency on STUbL activity for DNA repair. Based on these and other data, we propose that a critical role of STUbL is to antagonize DDR-inhibitory SUMO chain formation at DNA lesions. In this regard, we identify a SUMO-binding Swi2/Snf2 translocase called Rrp2 (ScUls1) as a mediator of the DDR defects in STUbL mutant cells. Therefore, in support of our proposal, SUMO chains attract activities that can antagonize STUbL and other DNA repair factors. Finally, we find that Taz1TRF1/TRF2-deficiency triggers extensive telomeric poly-SUMOylation. In this setting STUbL, together with its cofactor Cdc48p97, actually promotes genomic instability caused by the aberrant processing of taz1Δ telomeres by DNA repair factors. In summary, depending on the nature of the initiating DNA lesion, STUbL activity can either be beneficial or harmful.

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Taz1 Enforces Cell-Cycle Regulation of Telomere Synthesis

Cited by 39 publications

References 67 publications

Minishelterins separate telomere length regulation and end protection in fission yeast

Minishelterins separate telomere length regulation and end protection in fission yeast

Identification of the Functional Domains of the Telomere Protein Rap1 in Schizosaccharomyces pombe

SUMO-targeted ubiquitin ligase activity can either suppress or promote genome instability, depending on the nature of the DNA lesion

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