A SUMO and ubiquitin code coordinates protein traffic at replication factories

Lecona, Emilio; Fernández-Capetillo, Óscar

doi:10.1002/bies.201600129

Cited by 14 publications

(12 citation statements)

References 99 publications

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“…USP7 was identified as a DUB that removes ubiquitin from SUMO. Intriguingly, upon USP7 inhibition, SUMOylated proteins are collectively displaced from the replisome, which fully abrogates DNA replication, both by limiting fork progression and the firing of new origins (Lecona and Fernandez-Capetillo, 2016;.…”

Section: Sumo Chains At Replisomesmentioning

confidence: 99%

“…Ulp2, as well as SENP6 and SENP7 preferentially act on SUMO chains thereby countering the StUbL pathway. While SENP6 and SENP7 antagonize the StUbL pathway by limiting SUMO chain formation, two deubiquitylating enzymes, namely USP7 and USP11, possibly counter RNF4 signaling by catalyzing the removal of ubiquitin from SUMO2 polymers (Hendriks et al, 2015;Lecona and Fernandez-Capetillo, 2016;.…”

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confidence: 99%

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SUMO Chains Rule on Chromatin Occupancy

Keiten-Schmitz

Schunck

2020

Front. Cell Dev. Biol.

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The dynamic and reversible post-translational modification of proteins and protein complexes with the ubiquitin-related SUMO modifier regulates a wide variety of nuclear functions, such as transcription, replication and DNA repair. SUMO can be attached as a monomer to its targets, but can also form polymeric SUMO chains. While monoSUMOylation is generally involved in the assembly of protein complexes, multi-or polySUMOylation may have very different consequences. The evolutionary conserved paradigmatic signaling process initiated by multi-or polySUMOylation is the SUMO-targeted Ubiquitin ligase (StUbL) pathway, where the presence of multiple SUMO moieties primes ubiquitylation by the mammalian E3 ubiquitin ligases RNF4 or RNF111, or the yeast Slx5/8 heterodimer. The mammalian SUMO chain-specific isopeptidases SENP6 or SENP7, or yeast Ulp2, counterbalance chain formation thereby limiting StUbL activity. Many facets of SUMO chain signaling are still incompletely understood, mainly because only a limited number of polySUMOylated substrates have been identified. Here we summarize recent work that revealed a highly interconnected network of candidate polySUMO modified proteins functioning in DNA damage response and chromatin organization. Based on these datasets and published work on distinct polySUMO-regulated processes we discuss overarching concepts in SUMO chain function. We propose an evolutionary conserved role of polySUMOylation in orchestrating chromatin dynamics and genome stability networks by balancing chromatin-residency of protein complexes. This concept will be exemplified in processes, such as centromere/kinetochore organization, sister chromatid cohesion, DNA repair and replication.

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Section: Sumo Chains At Replisomesmentioning

confidence: 99%

mentioning

confidence: 99%

SUMO Chains Rule on Chromatin Occupancy

Keiten-Schmitz

Schunck

2020

Front. Cell Dev. Biol.

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“…71 Hence, SUMO-dependent deubiquitylation might be an effective means of generating and maintaining a Ubiquitin-poor environment at sites of DNA replication as recently suggested. 70,72 Further, USP7 disassembles Rad18-dependent poly-ubiquitin chains and compromises UVinduced PCNA mono-ubiquitylation in the DNA damage tolerance pathway. [73][74][75] As detailed below, USP7 operates with UVSSA during TC-NER.…”

Section: Regulation Of Poly-ubiquitylation By Parylation and Deubiquimentioning

confidence: 99%

Timing of DNA lesion recognition: Ubiquitin signaling in the NER pathway

Chitale

Richly

2016

Cell Cycle

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Damaged DNA is repaired by specialized repair factors that are recruited in a well-orchestrated manner to the damage site. The DNA damage response at UV inflicted DNA lesions is accompanied by posttranslational modifications of DNA repair factors and the chromatin environment sourrounding the lesion. In particular, mono- and poly-ubiquitylation events are an integral part of the DNA damage signaling. Whereas ubiquitin signaling at DNA doublestrand breaks has been subject to intensive studies comparatively little is known about the intricacies of ubiquitylation events occurring during nucleotide excision repair (NER), the major pathway to remove bulky helix lesions. Both, the global genomic (GG-NER) and the transcription-coupled (TC-NER) branches of NER are subject to ubiquitylation and deubiquitylation processes.Here we summarize our current knowledge of the ubiquitylation network that drives DNA repair in the NER pathway and we discuss the crosstalk of ubiquitin signaling with other prominent post-translational modfications that might be essential to time the DNA damage recognition step.

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“…Although the exact functions of replisome SUMOylation remain to be elucidated, a recent report showed that the SUMOylation of the catalytic subunit of DNA polymerase ε is important for DNA replication in yeast [64,65]. In addition to the SUMOylation of specific factors, we have proposed that the collective SUMOylation of the replication machinery supports DNA replication by creating an environment that facilitates interactions among replication factors [84], analogous to the SUMO-based group modification model proposed by Stefan Jentsch for DNA repair [85]. Within this model, we previously showed that USP7 is a SUMO-dependent deubiquitinase that maintains low levels of ubiquitination in the replisome, and whose action is necessary to sustain DNA replication [24].…”

Section: Sumo and Ubiquitin In Dna Replicationmentioning

confidence: 99%

“…The ubiquitination of the CMG could also be limited by specific DUBs, and we have previously identified USP7 as a SUMO-specific deubiquitinase that maintains a SUMO-rich/ubiquitin-poor environment at the DNA replication forks [24,81]. In this sense, SUMO could act as a signal to drive the ubiquitination of replication factors upon DNA replication termination or compete for ubiquitination to prevent the untimely modification of these proteins [84]. In yeast, the MCM2-7 complex has been shown to be SUMOylated in G1, and MCM7 SUMOylation persists during the S phase [66].…”

Section: Replisome Disassembly At the End Of Dna Replicationmentioning

confidence: 99%

Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1

Galarreta

Valledor

Fernández-Capetillo

et al. 2021

IJMS

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Post-translational modification of the DNA replication machinery by ubiquitin and SUMO plays key roles in the faithful duplication of the genetic information. Among other functions, ubiquitination and SUMOylation serve as signals for the extraction of factors from chromatin by the AAA ATPase VCP. In addition to the regulation of DNA replication initiation and elongation, we now know that ubiquitination mediates the disassembly of the replisome after DNA replication termination, a process that is essential to preserve genomic stability. Here, we review the recent evidence showing how active DNA replication restricts replisome ubiquitination to prevent the premature disassembly of the DNA replication machinery. Ubiquitination also mediates the removal of the replisome to allow DNA repair. Further, we discuss the interplay between ubiquitin-mediated replisome disassembly and the activation of CDK1 that is required to set up the transition from the S phase to mitosis. We propose the existence of a ubiquitin–CDK1 relay, where the disassembly of terminated replisomes increases CDK1 activity that, in turn, favors the ubiquitination and disassembly of more replisomes. This model has important implications for the mechanism of action of cancer therapies that induce the untimely activation of CDK1, thereby triggering premature replisome disassembly and DNA damage.

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A SUMO and ubiquitin code coordinates protein traffic at replication factories

Cited by 14 publications

References 99 publications

SUMO Chains Rule on Chromatin Occupancy

SUMO Chains Rule on Chromatin Occupancy

Timing of DNA lesion recognition: Ubiquitin signaling in the NER pathway

Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1

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