End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1

Lescasse, Rachel; Pobiega, Sabrina; Callebaut, Isabelle; Marcand, Stéphane

doi:10.1038/emboj.2013.24

Cited by 45 publications

(53 citation statements)

References 53 publications

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“…Sumoylation of K240/246 of Rap1 was recently shown to be important for telomere homeostasis (Lescasse et al 2013). However, we found that preventing sumoylation of these two lysine residues, as well as various combinations of other N-terminal and C-terminal residues, had no effect on Rap1 sumoylation, RPG transcription, and cell viability.…”

Section: Discussionmentioning

confidence: 99%

“…3A, bottom). Interestingly, several reports have indicated that Rap1 may be a Sumo target, although its relevance for transcription was never explored (Wohlschlegel et al 2004;Denison et al 2005;Hang et al 2011;Lickwar et al 2012;Albuquerque et al 2013;Lescasse et al 2013). Encouraged by these findings, we decided to focus on sumoylation of Rap1 at RPG promoters.…”

Section: Sumoylation At Rpgs Occurs At Rap1 Binding Sitesmentioning

confidence: 99%

“…4C for an overview of rap1 mutants used in this study) was shown to be important for telomere homeostasis (Lescasse et al 2013). However, we found that mutation of these sites did not affect Rap1 sumoylation (Fig.…”

Section: Sumoylation Of Rap1 Is Required For Transcription Of Rpgsmentioning

confidence: 99%

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Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes

Chymkowitch

Aanes

et al. 2015

Genome Res.

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Transcription factors are abundant Sumo targets, yet the global distribution of Sumo along the chromatin and its physiological relevance in transcription are poorly understood. Using Saccharomyces cerevisiae, we determined the genome-wide localization of Sumo along the chromatin. We discovered that Sumo-enriched genes are almost exclusively involved in translation, such as tRNA genes and ribosomal protein genes (RPGs). Genome-wide expression analysis showed that Sumo positively regulates their transcription. We also discovered that the Sumo consensus motif at RPG promoters is identical to the DNA binding motif of the transcription factor Rap1. We demonstrate that Rap1 is a molecular target of Sumo and that sumoylation of Rap1 is important for cell viability. Furthermore, Rap1 sumoylation promotes recruitment of the basal transcription machinery, and sumoylation of Rap1 cooperates with the target of rapamycin kinase complex 1 (TORC1) pathway to promote RPG transcription. Strikingly, our data reveal that sumoylation of Rap1 functions in a homeostatic feedback loop that sustains RPG transcription during translational stress. Taken together, Sumo regulates the cellular translational capacity by promoting transcription of tRNA genes and RPGs.

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Section: Discussionmentioning

confidence: 99%

Section: Sumoylation At Rpgs Occurs At Rap1 Binding Sitesmentioning

confidence: 99%

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Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes

Chymkowitch

Aanes

et al. 2015

Genome Res.

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“…Uls1 interacts with SUMO and Ubc4, the E2 ubiquitin-conjugating enzyme, while uls1D cells accumulate high-molecular-weight SUMO conjugates, which led to its classification as a SUMO-targeted ubiquitin ligase (STUbL) (Uzunova et al 2007). Additionally, Uls1 was proposed to function in nonhomologous end joining inhibition by dislodging poly-SUMOylated Rap1 molecules from telomeres (Lescasse et al 2013). However, enzymatic activity of Uls1 has never been biochemically demonstrated and little is known about its targets.…”

mentioning

confidence: 99%

“…Importantly, roles of Uls1 in DNA metabolism require an ATP-dependent translocase activity, RING domain, and SIMs (Cal-Bąkowska et al 2011;Chi et al 2011;Lescasse et al 2013;Tan et al 2013;Kramarz et al 2014). It can therefore be hypothesized that Uls1 may regulate DNA-repair-pathway choice at the sites of replication-associated DNA damage by modifying SUMOylation status and thus the abundance and/or activities of its target proteins.…”

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confidence: 99%

DNA Damage Tolerance Pathway Choice Through Uls1 Modulation of Srs2 SUMOylation in Saccharomyces cerevisiae

et al. 2017

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DNA damage tolerance and homologous recombination pathways function to bypass replication-blocking lesions and ensure completion of DNA replication. However, inappropriate activation of these pathways may lead to increased mutagenesis or formation of deleterious recombination intermediates, often leading to cell death or cancer formation in higher organisms. Post-translational modifications of PCNA regulate the choice of repair pathways at replication forks. Its monoubiquitination favors translesion synthesis, while polyubiquitination stimulates template switching. Srs2 helicase binds to small ubiquitin-related modifier (SUMO)-modified PCNA to suppress a subset of Rad51-dependent homologous recombination. Conversely, SUMOylation of Srs2 attenuates its interaction with PCNA Sgs1 helicase and Mus81 endonuclease are crucial for disentanglement of repair intermediates at the replication fork. Deletion of both genes is lethal and can be rescued by inactivation of Rad51-dependent homologous recombination. Here we show that Uls1, a member of the Swi2/Snf2 family of ATPases and a SUMO-targeted ubiquitin ligase, physically interacts with both PCNA and Srs2, and promotes Srs2 binding to PCNA by downregulating Srs2-SUMO levels at replication forks. We also identify deletion of as a suppressor of ΔΔ synthetic lethality and hypothesize that Δ mutation results in a partial inactivation of the homologous recombination pathway, detrimental in cells devoid of both Sgs1 and Mus81 We thus propose that Uls1 contributes to the pathway where intermediates generated at replication forks are dismantled by Srs2 bound to SUMO-PCNA. Upon deletion, accumulating Srs2-SUMO-unable to bind PCNA-takes part in an alternative PCNA-independent recombination repair salvage pathway(s).

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SUMO in the regulation of DNA repair and transcription at nuclear pores

Gasser,

Stutz

2023

FEBS Letters

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Two related post‐translational modifications, the covalent linkage of Ubiquitin and the Small Ubiquitin‐related MOdifier (SUMO) to lysine residues, play key roles in the regulation of both DNA repair pathway choice and transcription. Whereas ubiquitination is generally associated with protein degradation, the impact of sumoylation has been more mysterious. Sumoylation effects are largely mediated by the subnuclear localization of its targets, particularly in response to DNA damage. This is governed in part by the concentration of SUMO protease at nuclear pores (1,2). We review here the roles of sumoylation in determining subnuclear locus positioning relative to the nuclear envelope and the nuclear envelope to facilitate repair and to regulate transcription.

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End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1

Cited by 45 publications

References 53 publications

Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes

Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes

DNA Damage Tolerance Pathway Choice Through Uls1 Modulation of Srs2 SUMOylation in Saccharomyces cerevisiae

SUMO in the regulation of DNA repair and transcription at nuclear pores

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