ArticleCurrent genetics2018
Fumarase is involved in DNA double-strand break resection through a functional interaction with Sae2.
Article in Current genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- TPI and GAPDH Interact with Rad9, Linking Glycolytic Enzymes to Cancer.International journal of molecular sciences · 2026Article
- Methanotroph Methylotuvimicrobium alcaliphilum 20Z-3E as a fumarate producer: transcriptomic analysis and the role of malic enzyme.International microbiology : the official journal of the Spanish Society for Microbiology · 2025Article
- FpFumB Is Required for Basic Biological Processes and Virulence inMicroorganisms · 2025Article
- Privileged proteins with a second residence: dual targeting and conditional re-routing of mitochondrial proteins.The FEBS journal · 2024Review
- Tricarboxylic Acid Cycle Relationships with Non-Metabolic Processes: A Short Story with DNA Repair and Its Consequences on Cancer Therapy Resistance.International journal of molecular sciences · 2024Review
- The Pleiotropic Effects of Fumarate: From Mitochondrial Respiration to Epigenetic Rewiring and DNA Repair Mechanisms.Metabolites · 2023Review
- Article
- Macrosphelide A Exhibits a Specific Anti-Cancer Effect by Simultaneously Inactivating ENO1, ALDOA, and FH.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Mitochondrial Tumor Suppressors-The Energetic Enemies of Tumor Progression.Cancer research · 2021Review
- A combination of Class-I fumarases and metabolites (α-ketoglutarate and fumarate) signal the DNA damage response inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cell Metabolism and DNA Repair Pathways: Implications for Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Hereditary Leiomyomatosis and Renal Cell Cancer: Recent Insights Into Mechanisms and Systemic Treatment.Frontiers in oncology · 2021Review
- Genome Profiling for Aflatoxin BG3 (Bethesda, Md.) · 2020Article
- Distinct associations of the Saccharomyces cerevisiae Rad9 protein link Mac1-regulated transcription to DNA repair.Current genetics · 2020Article
- A role for the yeast PCNA unloader Elg1 in eliciting the DNA damage checkpoint.Current genetics · 2020Review
- Carbon catabolite repression: not only for glucose.Current genetics · 2019Review
- Chaperoning RPA during DNA metabolism.Current genetics · 2019Review
- Article
- The Yeast PCNA Unloader Elg1 RFC-Like Complex Plays a Role in Eliciting the DNA Damage Checkpoint.mBio · 2019Article
- Keep moving and stay in a good shape to find your homologous recombination partner.Current genetics · 2019Review
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the most severe forms of DNA damage is the double-strand break (DSB). Failure to properly repair the damage can cause mutation, gross chromosomal rearrangements and lead to the development of cancer. In eukaryotes, homologous recombination (HR) and non-homologous end joining (NHEJ) are the main DSB repair pathways. Fumarase is a mitochondrial enzyme which functions in the tricarboxylic acid cycle. Intriguingly, the enzyme can be readily detected in the cytosolic compartment of all organisms examined, and we have shown that cytosolic fumarase participates in the DNA damage response towards DSBs. In human cells, fumarase was shown to be involved in NHEJ, but it is still unclear whether fumarase is also important for the HR pathway. Here we show that the depletion of cytosolic fumarase in yeast prolongs the presence of Mre11 at the DSBs, and decreases the kinetics of repair by the HR pathway. Overexpression of Sae2 endonuclease reduced the DSB sensitivity of the cytosolic fumarase depleted yeast, suggesting that Sae2 and fumarase functionally interact. Our results also suggest that Sae2 and cytosolic fumarase physically interact in vivo. Sae2 has been shown to be important for the DSB resection process, which is essential for the repair of DSBs by the HR pathway. Depletion of cytosolic fumarase inhibited DSB resection, while the overexpression of cytosolic fumarase or Sae2 restored resection. Together with our finding that cytosolic fumarase depletion reduces Sae2 cellular amounts, our results suggest that cytosolic fumarase is important for the DSB resection process by regulating Sae2 levels.
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