Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair
Open accessAbstract
Protein modification by SUMO affects a wide range of protein substrates. Surprisingly, although SUMO pathway mutants display strong phenotypes, the function of individual SUMO modifications is often enigmatic, and SUMOylation-defective mutants commonly lack notable phenotypes. Here, we use DNA double-strand break repair as an example and show that DNA damage triggers a SUMOylation wave, leading to simultaneous multisite modifications of several repair proteins of the same pathway. Catalyzed by a DNA-bound SUMO ligase and triggered by single-stranded DNA, SUMOylation stabilizes physical interactions between the proteins. Notably, only wholesale elimination of SUMOylation of several repair proteins significantly affects the homologous recombination pathway by considerably slowing down DNA repair. Thus, SUMO acts synergistically on several proteins, and individual modifications only add up to efficient repair. We propose that SUMOylation may thus often target a protein group rather than individual proteins, whereas localized modification enzymes and highly specific triggers ensure specificity.
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The model of the Siz2 and Mms21 SUMO ligase complex suggests that both E3s could act jointly to modify DNA associated substrates perhaps through the DNA binding SAP domain of Siz2 or involving the Mms21 (Nse2) containing Smc5-6 complex.
“Our model of the Siz2 and Mms21 SUMO ligase complex (fig. S21A) suggests that both E3s could act jointly to modify DNA associated substrates perhaps through the DNA binding SAP domain of Siz2 (53) or involving the Mms21 (Nse2) containing Smc5–6 complex which modulates DNA recombination, replication and repair (54,55).”
From Computed structures of core eukaryotic protein complexes (2021) · cites this paper as [53]
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- Authors
- Psakhye, I., & Jentsch, S.
- Affiliations
- Max Planck Institute of Biochemistry (DE)
- Max Planck Society (DE)
- Corresponding author
- Jentsch, Stefan
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 151
- Issue
- 4
- Pages
- 807-820
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2039741753
- Cited by
- 484
- References
- 71
- Citations by year
- 2026: 9 · 2025: 31 · 2024: 34 · 2023: 24 · 2022: 26 · 2021: 43 · 2020: 31 · 2019: 42 · 2018: 33 · 2017: 42 · 2016: 53 · 2015: 49 · 2014: 34 · 2013: 33
- FWCI
- 14.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Max-Planck-Gesellschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- SUMOylation, DNA double-strand break repair, homologous recombination, SUMO ligase, single-stranded DNA, protein-protein interaction, protein stability, DNA damage response, post-translational modification
- MeSH terms
- Protein Processing, Post-Translational, Proteins, Saccharomyces cerevisiae, SUMO-1 Protein, Saccharomyces cerevisiae Proteins, DNA Breaks, Single-Stranded, Sumoylation, Recombinational DNA Repair
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