Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase
| Autor: | Raveendra B. Mokhamatam, Shubhrima Ghosh, Jagadeesh C. Bose K, Sudit S. Mukhopadhyay, Bishwajit Singh Kapoor, Kamal Mandal, Sunil K. Manna |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Genome instability
Iron-Sulfur Proteins DNA Repair DNA damage DNA repair Down-Regulation Mitochondrion Genomic Instability 03 medical and health sciences 0302 clinical medicine FANCG Fanconi anemia hemic and lymphatic diseases Cell Line Tumor Iron-Binding Proteins FANCD2 medicine Humans Amino Acid Sequence Fanconi Anemia Complementation Group G Protein Molecular Biology 030304 developmental biology 0303 health sciences biology Cell Biology medicine.disease Fanconi Anemia Complementation Group Proteins Cell biology Mitochondria Oxidative Stress Fanconi Anemia HEK293 Cells 030220 oncology & carcinogenesis Frataxin biology.protein Reactive Oxygen Species RNA Helicases Research Article DNA Damage HeLa Cells Signal Transduction |
| Zdroj: | Mol Cell Biol |
| Popis: | Fanconi anemia (FA) is a unique DNA damage repair pathway. To date, 22 genes have been identified that are associated with the FA pathway. A defect in any of those genes causes genomic instability, and the patients bearing the mutation become susceptible to cancer. In our earlier work, we identified that Fanconi anemia protein G (FANCG) protects the mitochondria from oxidative stress. In this report, we have identified eight patients having a mutation (C.65G>C), which converts arginine at position 22 to proline (p.Arg22Pro) in the N terminus of FANCG. The mutant protein, hFANCGR22P, is able to repair the DNA and able to retain the monoubiquitination of FANCD2 in the FANCGR22P/FGR22P cell. However, it lost mitochondrial localization and failed to protect mitochondria from oxidative stress. Mitochondrial instability in the FANCGR22P cell causes the transcriptional downregulation of mitochondrial iron-sulfur cluster biogenesis protein frataxin (FXN) and the resulting iron deficiency of FA protein FANCJ, an iron-sulfur-containing helicase involved in DNA repair. |
| Databáze: | OpenAIRE |
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