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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.

12Fanconi anemia (FA) is a unique DNA damage repair pathway. Almost twenty-two genes have 13 been identified which are associated with the FA pathway. Defect in any of those genes causes 14 genomic instability, and the patients bear the mutation become susceptible to cancer. In our 15 earlier work, we have identified that Fanconi anemia protein G (FANCG) protects the 16 mitochondria from oxidative stress. In this report, we have identified eight patients having 17 mutation (C.65G>C; p.Arg22Pro) in the N-terminal of FANCG. The mutant protein 18 hFANCGR22P is able to repair the DNA and able to retain the monoubiquitination of FANCD2 19 in FANCGR22P/FGR22P cell. However, it lost mitochondrial localization and failed to protect 20 mitochondria from oxidative stress. Mitochondrial instability in the FANCGR22P cell causes the 21 transcriptional down-regulation of mitochondrial iron-sulphur cluster biogenesis protein Frataxin 22 (FXN) and resulting iron deficiency of FA protein FANCJ, an iron-sulphur containing helicase 23 involved in DNA repair. 24 25 26 27 28 29 30 31 32 33 34 65 head and neck cancer (Rosenberg et al., 2005). To date, twenty two genes have been identified 66 that associate with FA that are primarily involved in a specific type of DNA damage repair; inter-67 strand crosslink (ICL) repair. ICL is caused by the exogenous alkylating agents or endogenous 68 130 tracker (pDsmito-Red) was used in these co-localization studies. Each deletion construct 131 including a wild type control was transiently expressed along with mito-tracker in HeLa cells. The 132 expression of both the constructs was analyzed by deconvolution microscope (Axio Observer.Z1, 133

Efficient conversion of lignocellulosic biomass into fermentable sugar is a bottleneck for cheap production of bio-ethanol. Recently identified enzyme Lytic Polysaccharide Monooxygenase (LPMO) family has brought new hope because of its boosting capabilities of cellulose hydrolysis. Cellulase enzymes of Aspergillus origin are important for their thermostable nature. Here we have identified and characterized a new class of auxiliary (AA16) oxidative enzyme LPMO from the genome of a locally isolated thermophilic fungus Aspergillus fumigatus (NITDGPKA3). The biochemical, structural, and biomass conversion efficiency of AfLPMO16 have been explored. The AfLPMO16 is an intronless gene and encodes the protein of about 29kDa of molecular weight. Sequence-wise it is close to C1 type and structurally it is similar to AA11 family of LPMOs. The structure exclusively consists of loops and sheets. The gene was expressed under inducible promoter (AOX1) with C-terminal His tag in the Pichia pastoris. The protein was purified, and enzyme kinetics was studied with 2, 6-DMP. Polysaccharides hydrolysis activity was observed with Carboxymethyl cellulose (CMC) and Phosphoric acid swollen cellulose (PASC). Further, the lignocellulosic biomass conversion enhancement with Cellulase cocktail gives 2-fold enhancement in reducing sugar release suggests the importance of AfLPMO16 in the bio-ethanol industry.

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