Advances in SUMO-based regulation of homologous recombination

Dhingra, Nalini; Zhao, Xiaolan

doi:10.1016/j.gde.2021.07.007

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…The SUMO system plays pivotal roles in orchestrating DNA damage responses (reviewed by Chang et al (2021 ), Da Costa and Schmidt (2020 ), and Dhingra and Zhao (2021 )). While a detailed discussion of all of these roles is beyond the scope of this article, it is to be expected that SUMO modification might play unique roles in the repair of TOP-DPCs.…”

Section: Sumoylation In the Repair Of Topoisomerase-mediated Dna Damagementioning

confidence: 99%

“…The normal biological function of topoisomerases may depend on their degradation (see, for example, Guturi et al (2016 )), and the repair pathways may represent extensions of pathways related to normal processes. As another speculative example of this way of thinking about topoisomerase degradation, TOP3 degradation appears to be important in appropriate resolution of recombination intermediates ( Dhingra and Zhao, 2021 ).…”

Section: Perspectives and Concluding Remarksmentioning

confidence: 99%

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SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases

Sun

Nitiss

Pommier

2022

Front. Mol. Biosci.

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Topoisomerases play crucial roles in DNA metabolism that include replication, transcription, recombination, and chromatin structure by manipulating DNA structures arising in double-stranded DNA. These proteins play key enzymatic roles in a variety of cellular processes and are also likely to play structural roles. Topoisomerases allow topological transformations by introducing transient breaks in DNA by a transesterification reaction between a tyrosine residue of the enzyme and DNA. The cleavage reaction leads to a unique enzyme intermediate that allows cutting DNA while minimizing the potential for damage-induced genetic changes. Nonetheless, topoisomerase-mediated cleavage has the potential for inducing genome instability if the enzyme-mediated DNA resealing is impaired. Regulation of topoisomerase functions is accomplished by post-translational modifications including phosphorylation, polyADP-ribosylation, ubiquitylation, and SUMOylation. These modifications modulate enzyme activity and likely play key roles in determining sites of enzyme action and enzyme stability. Topoisomerase-mediated DNA cleavage and rejoining are affected by a variety of conditions including the action of small molecules, topoisomerase mutations, and DNA structural forms which permit the conversion of the short-lived cleavage intermediate to persistent topoisomerase DNA–protein crosslink (TOP-DPC). Recognition and processing of TOP-DPCs utilizes many of the same post-translational modifications that regulate enzyme activity. This review focuses on SUMOylation of topoisomerases, which has been demonstrated to be a key modification of both type I and type II topoisomerases. Special emphasis is placed on recent studies that indicate how SUMOylation regulates topoisomerase function in unperturbed cells and the unique roles that SUMOylation plays in repairing damage arising from topoisomerase malfunction.

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Section: Sumoylation In the Repair Of Topoisomerase-mediated Dna Damagementioning

confidence: 99%

Section: Perspectives and Concluding Remarksmentioning

confidence: 99%

SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases

Sun

Nitiss

Pommier

2022

Front. Mol. Biosci.

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“…These misrepair events would give rise to genome rearrangements observable by one or more of the genome instability assays analyzed here. Repair-associated pathways, such as the DNA damage checkpoint, sumoylation by Mms21, SUMO-targeted ubiquitin ligation by the nuclear pore-associated Slx5-Slx8 complex, and protein degradation, have been implicated in the regulation of components of the fork repair processes outlined above ( Argunhan et al 2021 ; Cappadocia et al 2021 ; Dhingra and Zhao 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of different classes of genome instability suppressor genes through analysis of DNA damage response markers

Li,

Kolodner,

Putnam

2024

G3: Genes, Genomes, Genetics

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Cellular pathways that detect DNA damage are useful for identifying genes that suppress DNA damage, which can cause genome instability and cancer predisposition syndromes when mutated. We identified 199 high-confidence and 530 low-confidence DNA damage suppressing (DDS) genes in Saccharomyces cerevisiae through a whole genome screen for mutations inducing Hug1 expression, a focused screen for mutations inducing Ddc2 foci, and data from previous screens for mutations causing Rad52 foci accumulation and Rnr3 induction. We also identified 286 high-confidence and 394 low-confidence diverse genome instability suppressing (DGIS) genes through a whole genome screen for mutations resulting in increased gross chromosomal rearrangements and data from previous screens for mutations causing increased genome instability as assessed in a diversity of genome instability assays. Genes that suppress both pathways (DDS + DGIS+) prevent or repair DNA replication damage and likely include genes preventing collisions between the replication and transcription machineries. DDS + DGIS- genes, including many transcription-related genes, likely suppress damage that is normally repaired properly or prevent inappropriate signaling, whereas DDS- DGIS + genes, like PIF1, do not suppress damage but likely promote its proper, non-mutagenic repair. Thus, induction of DNA damage markers is not a reliable indicator of increased genome instability, and the DDS and DGIS categories define of mechanistically distinct groups of genes.

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“…HR is a less error-prone pathway restricted to S/G2-phases of the cell cycle, as it uses the sister chromatid as a homology template for repair. HR is the most intensely studied DDR pathway in the mammalian SUMO signalling field [ 55 ], with SUMOylation having important roles in DNA end-resection, DSB-chromatin signalling and RAD51 filament formation.…”

Section: Homologous Recombinationmentioning

confidence: 99%

SUMO and the DNA damage response

Bhachoo,

Garvin

2024

Biochemical Society Transactions

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The preservation of genome integrity requires specialised DNA damage repair (DDR) signalling pathways to respond to each type of DNA damage. A key feature of DDR is the integration of numerous post-translational modification signals with DNA repair factors. These modifications influence DDR factor recruitment to damaged DNA, activity, protein-protein interactions, and ultimately eviction to enable access for subsequent repair factors or termination of DDR signalling. SUMO1-3 (small ubiquitin-like modifier 1-3) conjugation has gained much recent attention. The SUMO-modified proteome is enriched with DNA repair factors. Here we provide a snapshot of our current understanding of how SUMO signalling impacts the major DNA repair pathways in mammalian cells. We highlight repeating themes of SUMO signalling used throughout DNA repair pathways including the assembly of protein complexes, competition with ubiquitin to promote DDR factor stability and ubiquitin-dependent degradation or extraction of SUMOylated DDR factors. As SUMO ‘addiction’ in cancer cells is protective to genomic integrity, targeting components of the SUMO machinery to potentiate DNA damaging therapy or exacerbate existing DNA repair defects is a promising area of study.

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Advances in SUMO-based regulation of homologous recombination

Cited by 6 publications

References 43 publications

SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases

SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases

Identification of different classes of genome instability suppressor genes through analysis of DNA damage response markers

SUMO and the DNA damage response

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