Cloned (Comment) | Organism |
---|---|
expressed in yeast FUM1 mutant strain | Homo sapiens |
mutant fumarase derivative lacking the MTS expressed in the FUM1 mutant strain, expressing the site-specific HO double-stranded DNA endonuclease | Saccharomyces cerevisiae |
Protein Variants | Comment | Organism |
---|---|---|
H153R | is catalytically inactive since it does not complement a fumarase knockout strain with respect to its TCA cycle function. Yeast strains expressing the mutant protein do not grow on glycerol as the sole energy and carbon source | Saccharomyces cerevisiae |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Saccharomyces cerevisiae | 5829 | - |
cytosol | under normal conditions | Homo sapiens | 5829 | - |
mitochondrion | - |
Saccharomyces cerevisiae | 5739 | - |
mitochondrion | under normal conditions | Homo sapiens | 5739 | - |
nucleus | after both hydroxyurea or ionizing radiation treatments, is localized in the nucleus after DNA damage | Homo sapiens | 5634 | - |
nucleus | is localized in the nucleus after DNA damage | Saccharomyces cerevisiae | 5634 | - |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Saccharomyces cerevisiae | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HCT-116 cell | - |
Homo sapiens | - |
HEK-293 cell | - |
Homo sapiens | - |
HeLa cell | - |
Homo sapiens | - |
Synonyms | Comment | Organism |
---|---|---|
fumarase | - |
Saccharomyces cerevisiae |
fumarate hydratase | - |
Homo sapiens |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | knock down of total cellular fumarate hydratase expression using specific shRNA | down |
Homo sapiens | fumarate hydratase levels increase 2fold after 24 h of treatment with double-strand breaks. Is overexpressed in response to DNA damage | up |
Saccharomyces cerevisiae | is overexpressed in response to DNA damage | up |
General Information | Comment | Organism |
---|---|---|
malfunction | in the absence of cytosolic fumarate hydratase, the cellular response to DNA damage is impaired | Homo sapiens |
malfunction | increased sensitivity (10-100fold) of the FUM1 mutant strain to ionizing radiation, to the presence of hydroxyurea and to double-strand breaks when compared to the wild-type. Cytosolic absence of fumarase in yeast with a DELTAfum1 chromosomal deletion can be complemented by human fumarase. Fumaric acid (25 mM) complements the phenotype of fumarase cytosolic absence. FUM1 mutant strain sensitivity to double-strand breaks can be complemented by catalytically active pDELTAMTS-FUM1 but not by the corresponding H153R mutant | Saccharomyces cerevisiae |
physiological function | cytosolic fumarase plays a role in the cellular response to double-strand breaks. Fumarase enzymatic activity is required for its DNA damage protective function. Fumarase activity is also required for the extra-mitochondrial function of fumarase | Saccharomyces cerevisiae |
physiological function | fumarate hydratase and fumaric acid are critical elements of the DNA damage response, which underlies the tumor suppressor role of fumarate hydratase and which is most probably independent of hypoxia-inducible factor. Cytoplasmic version of fumarate hydratase has a role in repairing DNA double-strand breaks in the nucleus. This role involves the movement of fumarate hydratase from the cytoplasm into the nucleus and depends on its enzymatic activity. When fumarate hydratase is absent from cells, its function in DNA repair can be substituted by high concentrations of one of the enzyme's products, fumaric acid. Fumarate hydratase deficiency leads to cancer because there is not enough fumaric acid in the nucleus to stimulate repair of DNA double-strand breaks. Can complement the cytosolic absence of fumarase in yeast with a DELTAfum1 chromosomal deletion | Homo sapiens |