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Literature summary for 4.2.1.2 extracted from

  • Yogev, O.; Yogev, O.; Singer, E.; Shaulian, E.; Goldberg, M.; Fox, T.D.; Pines, O.
    Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response (2010), PLoS Biol., 8, e1000328.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 4.2.1.2

Cloned(Commentary)

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

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

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

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Saccharomyces cerevisiae
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
HCT-116 cell
-
 Homo sapiens
-
HEK-293 cell
-
 Homo sapiens
-
HeLa cell
-
 Homo sapiens
-

Synonyms

Synonyms Comment Organism
fumarase
-
 Saccharomyces cerevisiae
fumarate hydratase
-
 Homo sapiens

Expression

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

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