Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase.

Autor:	K JCB; Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India., Kapoor BS; Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India., Mandal K; Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India., Ghosh S; Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India., Mokhamatam RB; Center for DNA Finger Printing and Diagnostics, Hyderabad, India., Manna SK; Center for DNA Finger Printing and Diagnostics, Hyderabad, India., Mukhopadhyay SS; Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India sudit.mukhopadhyay@bt.nitdgp.ac.in.
Jazyk:	angličtina
Zdroj:	Molecular and cellular biology [Mol Cell Biol] 2020 Nov 06; Vol. 40 (23). Date of Electronic Publication: 2020 Nov 06 (Print Publication: 2020).
DOI:	10.1128/MCB.00306-20
Abstrakt:	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. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
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