USP7 is a SUMO deubiquitinase essential for DNA replication

Lecona, Emilio; Rodríguez‐Acebes, Sara; Specks, Julia; López-Contreras, Andrés J.; Ruppen, Isabel; Murga, Matilde; Muñoz, Javier; Méndez, Juan Pablo; Fernández-Capetillo, Óscar

doi:10.1038/nsmb.3185

Cited by 128 publications

(150 citation statements)

References 76 publications

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“…For example, the Ataxin and USP11 deubiquitinases counteract the effects of RNF4 in maintaining PML and DNA repair protein sumoylation levels (Hendriks et al, 2015; Pfeiffer et al, 2017). During DNA replication, the USP7 deubiquitinase can remove ubiquitin conjugated to SUMO, thus preventing degradation of sumoylated proteins at chromatin around replisomes (Lecona et al, 2016). Functional studies suggest that these mechanisms are important for DNA repair and replication (Hendriks et al, 2015; Lecona et al, 2016; Pfeiffer et al, 2017).…”

Section: Global Changes In Sumoylation Levelsmentioning

confidence: 99%

“…During DNA replication, the USP7 deubiquitinase can remove ubiquitin conjugated to SUMO, thus preventing degradation of sumoylated proteins at chromatin around replisomes (Lecona et al, 2016). Functional studies suggest that these mechanisms are important for DNA repair and replication (Hendriks et al, 2015; Lecona et al, 2016; Pfeiffer et al, 2017). SUMO removal from substrates by desumoylases provides another way of counteracting the effects of STUbLs.…”

Section: Global Changes In Sumoylation Levelsmentioning

confidence: 99%

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SUMO-Mediated Regulation of Nuclear Functions and Signaling Processes

Zhao

2018

Molecular Cell

196

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Summary Since the discovery of SUMO twenty years ago, SUMO conjugation has become a widely-recognized post-translational modification that targets a myriad of proteins in many processes. Great progress has been made in understanding the SUMO pathway enzymes, substrate sumoylation, and the interplay between sumoylation and other regulatory mechanisms in a variety of contexts. As these research directions continue to generate insights into SUMO-based regulation, several mechanisms by which sumoylation and desumoylation can orchestrate large biological effects are emerging. These include the ability to target multiple proteins within the same cellular structure or process, respond dynamically to external and internal stimuli, and modulate signaling pathways involving other post-translational modifications. Focusing on nuclear function and intracellular signaling, this review highlights a broad spectrum of historical data and recent advances with the aim of providing an overview of mechanisms underlying SUMO-mediated global effects to stimulate further inquiry into intriguing roles of SUMO.

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Section: Global Changes In Sumoylation Levelsmentioning

confidence: 99%

Section: Global Changes In Sumoylation Levelsmentioning

confidence: 99%

SUMO-Mediated Regulation of Nuclear Functions and Signaling Processes

Zhao

2018

Molecular Cell

196

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“…USP7 was shown to establish the earlier observed SUMO-rich, ubiquitin-poor surroundings of replisomes by limiting ubiquitination of SUMOylated proteins, consistently hindering their clearance from the replication site. The authors also demonstrated that the clearance of the ubiquitinated SUMO conjugates was dependent on the action of the AAA-ATPase p97 (72). …”

Section: Sumo Is Involved In Proteostasis Via Crosstalk With Ubiquitinmentioning

confidence: 99%

“…The process of SUMO-dependent ubiquitination is being extensively explored, leading to the identification of enzymes involved in this crosstalk, like STUbLs and SUMO-targeted deubiquitinases. In mammals, two enzymes of each class have been identified (45, 72, 113, 118). Proteins that are misfolded or unfolded during stress are ubiquitinated and targeted to the proteasome.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Ubiquitin-dependent and independent roles of SUMO in proteostasis

Liebelt

Vertegaal

2016

American Journal of Physiology-Cell Physiology

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Cellular proteomes are continuously undergoing alterations as a result of new production of proteins, protein folding, and degradation of proteins. The proper equilibrium of these processes is known as proteostasis, implying that proteomes are in homeostasis. Stress conditions can affect proteostasis due to the accumulation of misfolded proteins as a result of overloading the degradation machinery. Proteostasis is affected in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and multiple polyglutamine disorders including Huntington's disease. Owing to a lack of proteostasis, neuronal cells build up toxic protein aggregates in these diseases. Here, we review the role of the ubiquitin-like posttranslational modification SUMO in proteostasis. SUMO alone contributes to protein homeostasis by influencing protein signaling or solubility. However, the main contribution of SUMO to proteostasis is the ability to cooperate with, complement, and balance the ubiquitin-proteasome system at multiple levels. We discuss the identification of enzymes involved in the interplay between SUMO and ubiquitin, exploring the complexity of this crosstalk which regulates proteostasis. These enzymes include SUMO-targeted ubiquitin ligases and ubiquitin proteases counteracting these ligases. Additionally, we review the role of SUMO in brain-related diseases, where SUMO is primarily investigated because of its role during formation of aggregates, either independently or in cooperation with ubiquitin. Detailed understanding of the role of SUMO in these diseases could lead to novel treatment options.

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“…The dataset reported by Lecona et al, illustrates the abundance ratio compression problem (Lecona et al, 2016). Only 31 proteins were found to be at least two-fold enriched on the nascent DNA with the highest log2 abundance ratio being 2.1 for PCNA.…”

Section: Replisome Purification Approachesmentioning

confidence: 99%

Proteomic Analyses of the Eukaryotic Replication Machinery

Chen¹

2017

Methods in Enzymology

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DNA replication in a human cell involves hundreds of proteins that copy the DNA accurately and completely each cell division cycle. In addition to the core DNA copying machine (the replisome), accessory proteins work to respond to replication stress, correct errors, and repackage the DNA into appropriate chromatin structures. New proteomic tools have been invented in the past few years to facilitate the purification, identification, and quantification of the replication, chromatin maturation, and replication stress response machineries. These tools, including iPOND (isolation of proteins on nascent DNA) and NCC (nascent chromatin capture), have yielded discoveries of new proteins involved in these processes and insights into the dynamic regulatory processes ensuring genome and chromatin integrity. In this review I will introduce these experimental approaches and examine how they have been utilized to define the replication fork proteome.

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USP7 is a SUMO deubiquitinase essential for DNA replication

Cited by 128 publications

References 76 publications

SUMO-Mediated Regulation of Nuclear Functions and Signaling Processes

SUMO-Mediated Regulation of Nuclear Functions and Signaling Processes

Ubiquitin-dependent and independent roles of SUMO in proteostasis

Proteomic Analyses of the Eukaryotic Replication Machinery

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