| http://purl.uniprot.org/citations/36030054 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36030054 | http://www.w3.org/2000/01/rdf-schema#comment | "TOP1MT encodes a mitochondrial topoisomerase that is important for mtDNA regulation and is involved in mitochondrial replication, transcription, and translation. Two variants predicted to affect TOP1MT function (V1 - R198C and V2 - V338L) were identified by exome sequencing of a newborn with hypertrophic cardiomyopathy. As no pathogenic TOP1MT variants had been confirmed previously, we characterized these variants for their ability to rescue several TOP1MT functions in KO cells. Consistent with these TOP1MT variants contributing to the patient phenotype, our comprehensive characterization suggests that both variants had impaired activity. Critically, we determined neither variant was able to restore steady state levels of mitochondrial-encoded proteins nor to rescue oxidative phosphorylation when re-expressed in TOP1MT KO cells. However, we found the two variants behaved differently in some respects; while the V1 variant was more efficient in restoring transcript levels, the V2 variant showed better rescue of mtDNA copy number and replication. These findings suggest that the different TOP1MT variants affect distinct TOP1MT functions. Altogether, these findings begin to provide insight into the many roles that TOP1MT plays in the maintenance and expression of the mitochondrial genome and how impairments in this important protein may lead to human pathology."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jbc.2022.102420"xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/author | "Zhang H."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/author | "Deng J."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/author | "Khan A."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/author | "Shutt T.E."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/author | "Pommier Y."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/author | "Huang S.N."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/author | "Kerr M."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/author | "Symes A."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/author | "Al Khatib I."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/pages | "102420"xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/title | "Functional characterization of two variants of mitochondrial topoisomerase TOP1MT that impact regulation of the mitochondrial genome."xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://purl.uniprot.org/core/volume | "298"xsd:string |
| http://purl.uniprot.org/citations/36030054 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/36030054 |
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