Myosin-like proteins 1 and 2 are not required for silencing or telomere anchoring, but act in the Tel1 pathway of telomere length control

Hediger, Florence; Dubrana, Karine; Gasser, Susan M.

doi:10.1016/s1047-8477(02)00533-6

Cited by 73 publications

(58 citation statements)

References 58 publications

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“…These telomeric clusters do not co-localize with nuclear pore complexes 17 . Intriguingly, the ability to survive a subtelomeric DSB is dependent on Nup84 as well as a number of factors known to anchor telomere clusters to the nuclear envelope 12,13,[18][19][20][21][22] .…”

mentioning

confidence: 81%

Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

et al. 2015

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DNA double-strand breaks (DSBs) are often targeted to nuclear pore complexes (NPCs) for repair. How targeting is achieved and the DNA repair pathways involved in this process remain unclear. Here, we show that the kinesin-14 motor protein complex (Cik1-Kar3) cooperates with chromatin remodellers to mediate interactions between subtelomeric DSBs and the Nup84 nuclear pore complex to ensure cell survival via break-induced replication (BIR), an error-prone DNA repair process. Insertion of a DNA zip code near the subtelomeric DSB site artificially targets it to NPCs hyperactivating this repair mechanism. Kinesin-14 and Nup84 mediate BIR-dependent repair at non-telomeric DSBs whereas perinuclear telomere tethers are only required for telomeric BIR. Furthermore, kinesin-14 plays a critical role in telomerase-independent telomere maintenance. Thus, we uncover roles for kinesin and NPCs in DNA repair by BIR and reveal that perinuclear telomere anchors license subtelomeric DSBs for this error-prone DNA repair mechanism.

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confidence: 81%

Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

et al. 2015

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“…This indicates that Ulp1 still localizes to the NPC in this mutant, although the NPCs themselves are mislocalized. Interestingly, these nup mutants, as well as mutants in MLP1 and MLP2, which are also involved in localization of Ulp1 to the NPC, have a variety of other phenotypes including defects in subtelomeric silencing, in repair of double-strand breaks near the telomere, and in tethering of telomeres to the nuclear envelope (Galy et al 2000;Hediger et al 2002;Therizols et al 2006). Some of these may also be secondary effects of their defects in SUMO metabolism and may be mechanistically related to the phenotypes of siz1D siz2D that we have characterized.…”

Section: Methodsmentioning

confidence: 99%

Topoisomerase I-Dependent Viability Loss in Saccharomyces cerevisiae Mutants Defective in Both SUMO Conjugation and DNA Repair

et al. 2007

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Siz1 and Siz2/Nfi1 are the two Siz/PIAS SUMO E3 ligases in Saccharomyces cerevisiae. Here we show that siz1D siz2D mutants fail to grow in the absence of the homologous recombination pathway or the Fen1 ortholog RAD27. Remarkably, the growth defects of mutants such as siz1D siz2D rad52D are suppressed by mutations in TOP1, suggesting that these growth defects are caused by topoisomerase I activity. Other mutants that affect SUMO conjugation, including a ulp1 mutant and the nuclear pore mutants nup60D and nup133D, show similar top1-suppressible synthetic defects with DNA repair mutants, suggesting that these phenotypes also result from reduced SUMO conjugation. siz1D siz2D mutants also display TOP1-independent genome instability phenotypes, including increased mitotic recombination and elongated telomeres. We also show that SUMO conjugation, TOP1, and RAD27 have overlapping roles in telomere maintenance. Top1 is sumoylated, but Top1 does not appear to be the SUMO substrate involved in the synthetic growth defects. However, sumoylation of certain substrates, including Top1 itself and Tri1 (YMR233W), is enhanced in the absence of Top1 activity. Sumoylation is also required for growth of top1D cells. These results suggest that the SUMO pathway has a complex effect on genome stability that involves several mechanistically distinct processes.

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“…There, the displacement of Ulp1 from NPCs affected sumoylation of yKu70, a key player in NHEJ. In mlp1/mlp2 mutants, it was shown that yKu70 function is impaired in DNA repair at telomeres (Hediger et al, 2002). It will therefore be interesting to see whether Tpr and Nup50 are also involved in NHEJ at telomeres in human cells.…”

Section: Other Nuclear Basket Nucleoporins and Ddrmentioning

confidence: 99%

“…Nup50 appears to be required for the nuclear import of XRCC1, which plays roles in single-strand break and base excision repair (Kirby et al, 2015). So far nothing is known about a putative role for Tpr in the DNA damage response (DDR), but yeast cells lacking Mlp1 and Mlp2, the yeast homologue of Tpr (Strambio-deCastillia et al, 1999), accumulate DNA damage and are highly sensitive to damaging drugs (Hediger et al, 2002;Palancade et al, 2007;Zhao et al, 2004). The role of Mlp1 and Mlp2 in DDR is not well characterised, but appears to be linked to their anchor function of the yeast SUMO-protease Ulp1 (Palancade et al, 2007;Zhao et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Localisation of Nup153 and SENP1 to nuclear pore complexes is required for 53BP1-mediated DNA double-strand break repair

Duhéron

Nilles

Pecenko

et al. 2017

Journal of Cell Science

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The nuclear basket of nuclear pore complexes (NPCs) is composed of three nucleoporins: Nup153, Nup50 and Tpr. Nup153 has a role in DNA double-strand break (DSB) repair by promoting nuclear import of 53BP1 (also known as TP53BP1), a mediator of the DNA damage response. Here, we provide evidence that loss of Nup153 compromises 53BP1 sumoylation, a prerequisite for efficient accumulation of 53BP1 at DSBs. Depletion of Nup153 resulted in reduced SUMO1 modification of 53BP1 and the displacement of the SUMO protease SENP1 from NPCs. Artificial tethering of SENP1 to NPCs restored non-homologous end joining (NHEJ) in the absence of Nup153 and re-established 53BP1 sumoylation. Furthermore, Nup50 and Tpr, the two other nuclear basket nucleoporins, also contribute to proper DSB repair, in a manner distinct from Nup153. Similar to the role of Nup153, Tpr is implicated in NHEJ and homologous recombination (HR), whereas loss of Nup50 only affects NHEJ. Despite the requirement of all three nucleoporins for accurate NHEJ, only Nup153 is needed for proper nuclear import of 53BP1 and SENP1-dependent sumoylation of 53BP1. Our data support the role of Nup153 as an important regulator of 53BP1 activity and efficient NHEJ.

show abstract

Myosin-like proteins 1 and 2 are not required for silencing or telomere anchoring, but act in the Tel1 pathway of telomere length control

Cited by 73 publications

References 58 publications

Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

Topoisomerase I-Dependent Viability Loss in Saccharomyces cerevisiae Mutants Defective in Both SUMO Conjugation and DNA Repair

Localisation of Nup153 and SENP1 to nuclear pore complexes is required for 53BP1-mediated DNA double-strand break repair

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