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 bearing the mutation become susceptible to cancer. In earlier work, the authors have identified that Fanconi anemia protein G (FANCG) protects the mitochondria from oxidative stress. In this report, eight patients having mutation (C.65G>C; p.Arg22Pro) in the N-terminal of FANCG were identified. 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.

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