Bose, K.J.C. and Kapoor, B.S. and Mondal, Kamal and Ghosh, Shubhrima and Mokhamatam, R.B. and Manna, S.K. and Mukhopadhyay, Sudit S. (2020) Loss of mitochondrial localization of human FANCG causes defective FANCJ helicase. Molecular and Cellular Biology, 40 (23). e00306-20. ISSN 0270-7306

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Abstract

Fanconi anemia (FA) is a unique DNA damage repair pathway. To date, twenty-two genes have been identified which are associated with the FA pathway. Defect in any of those genes causes genomic instability, and the patients bear the mutation become susceptible to cancer. In our earlier work, we have identified that Fanconi anemia protein G (FANCG) protects the mitochondria from oxidative stress. In this report, we have identified eight patients having mutation (C.65G>C; p.Arg22Pro) in the N-terminal of FANCG. The mutant protein hFANCGR22P is able to repair the DNA and able to retain the monoubiquitination of FANCD2 in 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 down-regulation of mitochondrial iron-sulfur cluster biogenesis protein Frataxin (FXN) and resulting iron deficiency of FA protein FANCJ, an iron-sulfur containing helicase involved in DNA repair.

Item Type:	Article
Subjects:	Molecular Biology
Depositing User:	Users 2 not found.
Date Deposited:	03 Oct 2020 19:24
Last Modified:	10 Nov 2020 18:28
URI:	http://cdfd.sciencecentral.in/id/eprint/976

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