Dr. Narottam Acharya

Academics

Degree	University/Institution
Ph. D., FNASc.	Dept. of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.

Work Experience

Position	University/Organisation	Period
Scientist-G	Institute of Life Sciences, Bhubaneswar, Odisha.	Since Feb. 2025
Scientist-F	Institute of Life Sciences, Bhubaneswar, Odisha.	Jan. 2021-Jan 2025
Scientist-E	Institute of Life Sciences, Bhubaneswar, Odisha.	Jan. 2016-Dec. 2020
Scientist-D	Institute of Life Sciences, Bhubaneswar, Odisha.	June 2011- Dec. 2015
Research Scientist	Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas	2009-2011
Post-Doctoral Fellow	Sealy center for Molecular Sciences, UTMB, Galveston, Texas	2003-2009

Awards & Recognition

Details
Association of Microbiologists of India (AMI)-Soshil Kumar Jain Panacea Biotech Award-2024 Invitee to Guha Research Conference-2024 at Kaziranga, Assam (2024) Elected Fellow of National Academy of Sciences, India (2023) Stood first class first in M. Sc. Awarded the fellowship of the Indian Institute of Science, Bangalore, India. Senior research fellowship from CSIR (Council of scientific and Industrial Research), Govt. of India. Attended “Young Investigator Meeting-2010, Kolkata”. Stood first class first in B.Sc. Editors in Indian Journal of Microbiology, Microbial Cell, and Frontiers in Fungal Biology

Details

Association of Microbiologists of India (AMI)-Soshil Kumar Jain Panacea Biotech Award-2024
Invitee to Guha Research Conference-2024 at Kaziranga, Assam (2024)
Elected Fellow of National Academy of Sciences, India (2023)
Stood first class first in M. Sc.
Awarded the fellowship of the Indian Institute of Science, Bangalore, India.
Senior research fellowship from CSIR (Council of scientific and Industrial Research), Govt. of India.
Attended “Young Investigator Meeting-2010, Kolkata”.
Stood first class first in B.Sc.
Editors in Indian Journal of Microbiology, Microbial Cell, and Frontiers in Fungal Biology

Research

Details
Genomic Instability and Diseases Research Summary: Replication of DNA strands during each cell division is a prerequisite and critical for proper functioning of any genome. It necessitates faithful duplication of the genetic content and ensures genome stability by preventing faulty DNA synthesis that could render spontaneous mutation, genome rearrangement, and DNA breaks. DNA polymerases (Pol) are the enzymes required for DNA synthesis virtually in all the DNA transaction pathways, and any abnormalities in Pol function has been shown to be associated with cell death, tumorigenesis, resistance to chemotherapeutics, and development of an array of complex diseases in humans. In microorganisms, genome instability is also linked to virulence and multidrug resistance. We focus on the mechanism of eukaryotic DNA replication and use both yeasts and human cells as our model systems. Genetic and biochemical studies in S. cerevisiae have indicated that the highly accurate and processive genomic DNA replication is carried out by the coordinated action of Polα-primase, Polδ and Polε (Biochemical Society Trans. 2020 and Current Genetics 2020). PCNA (the eukaryotic clamp loader) is an essential homotrimeric ring protein plays a critical role in orchestrating the assembly of replisome complex, recruiting DNA polymerases, and factors involved in DNA damage response, chromatin assembly and remodeling, and cell cycle control. Each of the PCNA-binding partners harbors a dedicated region called PCNA-interacting protein (PIP) motif. PIPs in all three subunits contribute to processive DNA synthesis by Polδ, and mutational inactivation of all three PIP motifs abrogates its ability to synthesize DNA with PCNA (PNAS, 2011). In human, unlike in yeast, Polδ is a pentameric holoenzyme consisting of p125, p50, p68, and dimeric p12 subunits. An amino-terminal dimerization and a carboxyl terminal PIP motifs in p12 have been mapped, and dimerization of p12 is critical for its interaction with PCNA (LSA, 2019). Although PCNA is a structurally conserved protein, complementation analyses suggest it to be highly species specific (BMC-Micro. 2015 and FEBS letters 2021). By using structural and mutational analyses, we find that the IDCL and J loop structures of PCNA are unique and responsible for cross-species incompatibility, therefore these regions may be targeted to develop species-specific inhibitors (JBC(a)-2021). DNA replication does not proceed smoothly, as it encounters both DNA lesions and non-B form of DNA structures that must be by-passed to prevent collapsing of replication fork. Trans-lesion DNA synthesis (TLS) polymerases are highly sophisticated enzymes can bypass certain lesions in DNA. DNA polymerase eta (Polη) is one such enzymes required for efficient bypass of UV- induced cyclobutane pyrimidine dimers in the genome. Additionally, Polη also possess non-TLS activities such as serum induced morphogenesis, amphotericin B drug resistance and virulence in pathogenic yeast Candida albicans (Molecular Micro.- 2018, Cellular Micro. 2019, and Current Genetics 2019). Further, we identify three distinct group of Polηs from species across kingdom based on their modes of PCNA interaction (JBC (b)-2021). Candida albicans survives as a commensal fungus in the gastrointestinal tract, and its excessive growth causing infections in immune-suppressed individuals is widely accepted. However, our recent data suggests a mutualism between the host and C. albicans. Dietary C. albicans does not cause any noticeable infections, rather it colonizes in the gut to modulate microbiome dynamics which in turn negates the high-fat diet induced uncontrolled body weight gain, metabolic hormonal imbalances, and inflammatory responses. Interestingly, adding C. albicans to a non-obesogenic diet stimulates the appetite regulated hormones and helped the mice gain healthy body weight (biorxiv-2022/M.Spectrum 2022). In its pathogenic state, C. albicans causes fatal systemic infections and are associated with a higher rate of morbidity and mortality, and represent major healthcare problems. Currently, chemotherapy is the sole available option for combating fungal diseases and no vaccine has been developed yet for human use (FCIM-2022). We have generated several genetically engineered knockout strains of C. albicans and also identified few of those strains to be attenuated (Gut microbes-2023). Two of such isolates [CNA94-Indian Patent Application No.: 202231013971 (JBC-2024-Cover page) and CNA25- Indian Patent Application No.: 202231043203 (EMBO Molecular Medicine)] have also been patented to explore further as a whole cell vaccine against fungal and other cross-species infections. In addition a detailed characterisations of EDTA-treated C. albicans cells both in vitro and pre-clinical models led to discovery of a potential live whole-cell vaccine against fungal infections *(Indian Patent Application No.: 202331056818, eLife-2024).*

Details

Genomic Instability and Diseases

Research Summary:

Replication of DNA strands during each cell division is a prerequisite and critical for proper functioning of any genome. It necessitates faithful duplication of the genetic content and ensures genome stability by preventing faulty DNA synthesis that could render spontaneous mutation, genome rearrangement, and DNA breaks. DNA polymerases (Pol) are the enzymes required for DNA synthesis virtually in all the DNA transaction pathways, and any abnormalities in Pol function has been shown to be associated with cell death, tumorigenesis, resistance to chemotherapeutics, and development of an array of complex diseases in humans. In microorganisms, genome instability is also linked to virulence and multidrug resistance. We focus on the mechanism of eukaryotic DNA replication and use both yeasts and human cells as our model systems. Genetic and biochemical studies in S. cerevisiae have indicated that the highly accurate and processive genomic DNA replication is carried out by the coordinated action of Polα-primase, Polδ and Polε (Biochemical Society Trans. 2020 and Current Genetics 2020). PCNA (the eukaryotic clamp loader) is an essential homotrimeric ring protein plays a critical role in orchestrating the assembly of replisome complex, recruiting DNA polymerases, and factors involved in DNA damage response, chromatin assembly and remodeling, and cell cycle control. Each of the PCNA-binding partners harbors a dedicated region called PCNA-interacting protein (PIP) motif. PIPs in all three subunits contribute to processive DNA synthesis by Polδ, and mutational inactivation of all three PIP motifs abrogates its ability to synthesize DNA with PCNA (PNAS, 2011). In human, unlike in yeast, Polδ is a pentameric holoenzyme consisting of p125, p50, p68, and dimeric p12 subunits. An amino-terminal dimerization and a carboxyl terminal PIP motifs in p12 have been mapped, and dimerization of p12 is critical for its interaction with PCNA (LSA, 2019). Although PCNA is a structurally conserved protein, complementation analyses suggest it to be highly species specific (BMC-Micro. 2015 and FEBS letters 2021). By using structural and mutational analyses, we find that the IDCL and J loop structures of PCNA are unique and responsible for cross-species incompatibility, therefore these regions may be targeted to develop species-specific inhibitors (JBC(a)-2021). DNA replication does not proceed smoothly, as it encounters both DNA lesions and non-B form of DNA structures that must be by-passed to prevent collapsing of replication fork. Trans-lesion DNA synthesis (TLS) polymerases are highly sophisticated enzymes can bypass certain lesions in DNA. DNA polymerase eta (Polη) is one such enzymes required for efficient bypass of UV- induced cyclobutane pyrimidine dimers in the genome. Additionally, Polη also possess non-TLS activities such as serum induced morphogenesis, amphotericin B drug resistance and virulence in pathogenic yeast Candida albicans (Molecular Micro.- 2018, Cellular Micro. 2019, and Current Genetics 2019). Further, we identify three distinct group of Polηs from species across kingdom based on their modes of PCNA interaction (JBC (b)-2021).

Candida albicans survives as a commensal fungus in the gastrointestinal tract, and its excessive growth causing infections in immune-suppressed individuals is widely accepted. However, our recent data suggests a mutualism between the host and C. albicans. Dietary C. albicans does not cause any noticeable infections, rather it colonizes in the gut to modulate microbiome dynamics which in turn negates the high-fat diet induced uncontrolled body weight gain, metabolic hormonal imbalances, and inflammatory responses. Interestingly, adding C. albicans to a non-obesogenic diet stimulates the appetite regulated hormones and helped the mice gain healthy body weight (biorxiv-2022/M.Spectrum 2022). In its pathogenic state, C. albicans causes fatal systemic infections and are associated with a higher rate of morbidity and mortality, and represent major healthcare problems. Currently, chemotherapy is the sole available option for combating fungal diseases and no vaccine has been developed yet for human use (FCIM-2022). We have generated several genetically engineered knockout strains of C. albicans and also identified few of those strains to be attenuated (Gut microbes-2023). Two of such isolates [CNA94-Indian Patent Application No.: 202231013971 (JBC-2024-Cover page) and CNA25- Indian Patent Application No.: 202231043203 (EMBO Molecular Medicine)] have also been patented to explore further as a whole cell vaccine against fungal and other cross-species infections. In addition a detailed characterisations of EDTA-treated C. albicans cells both in vitro and pre-clinical models led to discovery of a potential live whole-cell vaccine against fungal infections (Indian Patent Application No.: 202331056818, eLife-2024).

Publications

Details
Genomic Instability and Diseases Peer reviewed publications: Jugal Kishor Sahu, Shweta Thakur, Ipsita Subhadarsini, and Narottam Acharya (2024) p12 isoform-2 is a regulatory subunit of human DNA polymerase delta and is dysregulated in various cancers. FEBS Letters, doi.org/10.1002/1873-3468.15070. Bhabasha Gyanadeep Utkalaja, Shraddheya Kumar Patel, Satya Ranjan Sahu, Abinash Dutta, and Narottam Acharya (2024) Critical roles of Dpb3-Dpb4 sub-complex of DNA polymerase epsilon in DNA replication, genome stability, and pathogenesis of Candida albicans. mBio. doi.org/10.1128/mbio.01227-24. Satya Ranjan Sahu, Abinash Dutta, Doureradjou Peroumal, Premlata Kumari, Bhabasha Gyanadeep Utkalaja, Shraddheya Kumar Patel, and Narottam Acharya (2024) Immunogenicity and efficacy of CNA25 as a potential whole-cell vaccine against systemic candidiasis. EMBO Molecular Medicine.doi: 10.1038/s44321-024-00080-8. Bhabasha Gyanadeep Utkalaja, Satya Ranjan Sahu, Sushree Subhashree Parida, and Narottam Acharya (2024) Hsp90-mediated multi-drug resistance in DNA polymerase defective strains of Candida albicans. Journal of Fungi, 10, 222. https://doi.org/10.3390/jof10030222. Swagata Bose, Satya Ranjan Sahu, Abinash Dutta, and Narottam Acharya (2024) A chemically-induced attenuated strain of Candida albicans generates robust protective immune responses and prevents systemic candidiasis development. eLife, 13:RP93760. doi: 10.7554/eLife.93760. Satya Ranjan Sahu, Bhabasha Gyanadeep Utkalaja, Shraddheya Kumar Patel, and Narottam Acharya (2023) Spot Assay and Colony Forming Unit (CFU) Analyses-based sensitivity test for Candida albicans and Saccharomyces cerevisiae. Bio-protocol, 13(21):e4872. doi: 10.21769/BioProtoc.4872. Satya Ranjan Sahu, Shweta Thakur, Doureradjou Peroumal, Bhabasha Gyanadeep Utkalaja, Abinash Dutta, Premlata Kumari, Ipsita Subhadarsini, and Narottam Acharya (2023) 4-Nitroquinoline 1-oxide induces immune-cells death to onset early immunosuppression during Oral squamous cell carcinoma development. *Frontiers in Immunology, 14:1274519. doi: 10.3389/fimmu.2023.1274519. Shraddheya Kumar Patel, Satya Ranjan Sahu, and Narottam Acharya* (2023) Cell cycle Analysis of Candida albicans by Flow Cytometry. Bio-protocol, 13(20): e4748. DOI: 10.21769/BioProtoc.4748. Premlata Kumari, Satya Ranjan Sahu, Abinash Dutta, Bhabasha Gyanadeep Utkalaja, and Narottam Acharya (2023) RAD51-WSS1 dependent genetic pathways are essential for DNA-Protein crosslink repair and pathogenesis in Candida albicans. *Journal of Biological Chemistry, doi.org/10.1016/j.jbc.2023.104728. (On the cover page) Swagata Bose, Durg Vijai Singh, Tapan Kumar Adhya, and Narottam Acharya* (2023) Escherichia coli, but Not Staphylococcus aureus, Functions as a Chelating Agent That Exhibits Antifungal Activity against the Pathogenic Yeast Candida albicans. Journal of Fungi, 9, 286. https://doi.org/10.3390/jof9030286 Shraddheya Kumar Patel, Satya Ranjan Sahu, Bhabasha Gyanadeep Utkalaja, Swagata Bose, and Narottam Acharya (2023) Pol32, an accessory subunit of DNA polymerase delta, plays an essential role in genome stability and pathogenesis of Candida albicans. *Gut microbes, DOI: 10.1080/19490976.2022.2163840. Narottam Acharya, Louise Prakash, and Satya Prakash (2023) Yeast 9-1-1 complex acts as a sliding clamp for DNA synthesis by DNA polymerase ε. Journal of Biological Chemistry, Jan;299(1):102727. doi: 10.1016/j.jbc.2022.102727. Doureradjou Peroumal, Satya Ranjan Sahu, Premlata Kumari, Bhabasha G. Utkalaja, and Narottam Acharya* (2022) Commensal Fungus Candida albicans Maintains a Long-Term Mutualistic Relationship with the Host To Modulate Gut Microbiota and Metabolism. Microbiology Spectrum, DOI: 10.1128/spectrum.02462-22. Satya Ranjan Sahu, Swagata Bose, Manish Singh, Premlata Kumari, Abinash Dutta, Bhabasha G. Utkalaja, Shraddheya Kumar Patel, and Narottam Acharya (2022) Vaccines against Candidiasis: Status, Challenges and Emerging opportunity. *Front. Cell. Infect. Microbiol., DOI: 10.3389/fcimb.2022.1002406. Kodavati Manohar, Prashant Khandagale, Shraddheya Kumar Patel, Jugal Kishor Sahu, and Narottam Acharya* (2021) Ubiquitin-binding domain of DNA polymerase eta lacking the PCNA-interacting-protein motif directly binds to PCNA and regulates translesion DNA synthesis. *Journal of Biological Chemistry, Dec 18;298(2):101506. doi: 10.1016/j.jbc.2021.101506. Premlata Kumari, Rajivgandhi Sundaram, Kodavati Manohar, Dileep Vasudevan and Narottam Acharya* (2021) Interdomain connecting loop and J loop structures determine cross-species compatibility of PCNA. *Journal of Biological Chemistry, Jul;297(1):100911. doi: 10.1016/j.jbc.2021.100911. Rajivgandhi Sundaram, Kodavati Manohar, Shraddheya Kumar Patel, Narottam Acharya* and Dileep Vasudevan (2021) Structural analyses of PCNA from the fungal pathogen Candida albicans. *FEBS Letters, May;595(9):1328-1349. doi: 10.1002/1873-3468. Narottam Acharya, Shraddheya Kumar Patel, Satya Ranjan Sahu, and Premlata Kumari (2020) “PIPs” in DNA polymerase – PCNA interaction affairs. Biochem. Soci. Trans.* Nov 16:BST20200678. doi: 10.1042/BST20200678. Swagata Bose, Shifu Aggarwal, DurgVijai Singh and Narottam Acharya (2020) Extracellular vesicles: An emerging platform in gram-positive bacteria. Micro. cell Vol. 7, No. 12, pp. 312 – 322; doi: 10.15698/mic2020.12.737. Prashant Khandagale, Shweta Thakur and Narottam Acharya (2020) Identification of PCNA interacting protein motifs in human DNA polymerase delta, *Bioscience Reports, 40 (4). (doi.org/10.1042/BSR20200602) Narottam Acharya, Prashant Khandagale, Shweta Thakur, Jugal Kishor Sahu and Bhabasha Gyanadeep Utakalaja (2020) Quaternary structural diversity in Eukaryotic DNA Polymerases: Monomeric to Multimeric form. Current Genetics, Aug; 66 (4):635-655. doi: 10.1007/s00294-020-01071-1. Doureradjou Peroumal, Kodavati Manohar, Shraddheya Kumar Patel, Premlata Kumari, Satya Ranjan Sahu and Narottam Acharya* (2019) Virulence and pathogenicity of a Candida albicans mutant with reduced filamentation. *Cellular Microbiology,* 21 (12) (doi.org/10.1111/cmi.13103). Prashant Khandagale, Doureradjou Peroumal, Kodavati Manohar and Narottam Acharya (2019) Human DNA polymerase delta is a pentameric holoenzyme with a dimeric p12 subunit. *Life Science Alliance, Vol. 2, No., 2. (doi.org/10.26508/lsa.201900323) Narottam Acharya, Kodavati Manohar, D. Peroumal, Prashant Khandagale, Shraddheya Kumar Patel, Satya Ranjan Sahu, and Premlata Kumari (2019) Multifaceted activities of DNA Polymerase eta: Beyond translesion DNA synthesis. Curr. Genetics, 65(3), 649-656. (doi.org/10.1007/s00294-018-0918-5). Jingde, N., Ray, R., Sinha, S., Rana, K., Singh, S. K., Khandagale, P., Narottam Acharya* and V. Rai (2018) Cysteine mediated disulfide bond formation in RAGE V domain facilitates its functionally relevant dimerization. *Biochimie, 154, 55-61. Kodavati Manohar, Doureradjou Peroumal and Narottam Acharya* (2018) TLS dependent and independent functions of DNA polymerase eta (Polh/ Rad30) from Pathogenic Yeast Candida albicans. Molecular Microbiology, 110 (5), 707-727 Suresh Satpati, Kodavati Manohar, Narottam Acharya, Anshuman Dixit. (2017) Comparative molecular dynamics studies of heterozygous open reading frames of DNA polymerase eta (η) in pathogenic yeast Candida albicans. Sci Rep., 7:41087. doi: 10.1038/srep41087. (Joined corresponding author) Kodavati Manohar and Narottam Acharya (2015) Characterization of Proliferating Cell Nuclear Antigen (PCNA) from Pathogenic Yeast Candida albicans and its functional analyses in S. cerevisiae.* *BMC-Microbiology, 15:257. Yoon J.H⁺., Acharya N⁺.,* Jeseong P., Debashree Basu, Prakash S. and Prakash L. (2014) Identification of two functional PCNA binding domains in human DNA polymerase κ (+ joint first author). Genes to Cells., 19(7):594-601. Acharya N., Kalssen R., Johnson R.E., Prakash L. and Prakash S. (2011) PCNA binding domains in all three subunits of yeast DNA polymerase δ modulate its function in DNA replication. *Proc Natl Acad Sci USA., Nov.1; 108(44):17927-17932. Acharya N⁺.,* Yoon J.H⁺., Hutwitz J., Prakash L. and Prakash S. (2010) DNA polymerase eta lacking the ubiquitin-binding domain promotes replicative lesion bypass in human cells (⁺ joint first author). *Proc Natl Acad Sci USA., Jun 8; 107(23):10401-10405. Acharya N.,* Johnson R.E., Pagès V., Prakash L. and Prakash S. (2009) Yeast Rev1 protein promotes complex formation of DNA polymerase zeta with Pol32 subunit of DNA polymerase delta. *Proc Natl Acad Sci USA., Jun 16; 106(24):9631-9636. Acharya N.,* Yoon J.H., Gali H., Unk I., Haracska L., Johnson R.E., Hutwitz J., Prakash L. and Prakash S. (2008) Roles of PCNA-binding and ubiquitin-binding domains in human DNA polymerase eta in translesion DNA synthesis. *Proc Natl Acad Sci USA., Nov 18; 105 (46):17724-17729. Pagès V., Bresson A., Acharya N.,* Prakash L. Fuchs R.P. and Prakash S. (2008) Requirement of Rad5 for DNA polymerase zeta-dependent translesion synthesis in Saccharomyces cerevisiae. Genetics, 2008 Sep; 180(1):73-82. Acharya N., Haracska L., Prakash S. and Prakash L. (2007) Complex formation of yeast Rev1 with DNA polymerase {eta}. *Mol Cell Biol.,* Dec; 27 (23):8401-8408. Acharya N., Brahma A., Haracska L., Prakash S. and Prakash L. (2007) Mutations in the Ubiquitin Binding UBZ Motif of DNA Polymerase {eta} Do Not Impair Its Function in Translesion Synthesis during Replication. *Mol Cell Biol.,* Oct; 27(20):7266-7272. Acharya N., Johnson R.E., Prakash S. and Prakash L. (2006) Complex formation with Rev1 enhances the proficiency of Saccharomyces cerevisiae DNA polymerase zeta for mismatch extension and for extension opposite from DNA lesions. Mol. Cell Biol., Dec. 26 (24), 9555-9563. Acharya N., Haracska L., Johnson R.E., Unk I., Prakash S. and Prakash L. (2005) Complex formation of yeast Rev1 and Rev7 proteins: a novel role for the polymerase-associated domain. Mol. Cell Biol., Nov. 25 (21), 9734-9740. Haracska L., Acharya N., Unk I., Johnson R.E., Hurwitz J., Prakash L. and Prakash S. (2005) A single domain in human DNA polymerase iota mediates interaction with PCNA: implications for translesion DNA synthesis. Mol. Cell Biol., Feb. 25 (3), 1183-1190 Acharya N, Talawar R. K., Purnapatre K, Varshney U. (2004) Use of sequence microdivergence in mycobacterial ortholog to analyze contributions of the water-activating loop histidine of Escherichia coli uracil-DNA glycosylase in reactant binding and catalysis. *Biochem. Biophys. Res. Commun., 320(3), 893-899. Acharya, N., Talawar R. K., Saikrishnan, K., Vijayan, M and Varshney, U. (2003) Substitutions at tyrosine 66 of Escherichia coli uracil DNA glycosylase lead to characterization of an efficient enzyme that is recalcitrant to product inhibition. Nucleic Acids Res., 31(24), 7216-7226. Acharya, N., Kumar P. and Varshney, U. (2003) Complexes of Uracil-DNA glycosylase inhibitor protein, Ugi, with Mycobacterium smegmatis* and Mycobacterium tuberculosis uracil-DNA glycosylases. Microbiology 149, 1647-1658. Saikrishnan, K., Jeyakanthan, Venkatesh, J., Acharya, N., Purnapatre, K., Sekar, K., Varshney, U. and Vijayan, M. (2003) Structure of Mycobacterium tuberculosis single stranded DNA binding protein. Variability in quaternary structure and its implications. *J. Mol. Biol.,* 331, 385-393. Acharya, N., Roy, S., and Varshney, U. (2002) Mutational analysis of the uracil DNA glycosylase inhibitor protein and its interaction with Escherichia coli uracil DNA glycosylase. *J. Mol. Biol.,* 321 (4), 579-590. Acharya, N., and Varshney, U. (2002) Biochemical properties of single stranded DNA binding protein from Mycobacterium smegmatis, a fast growing mycobacterium and its physical and functional interaction with uracil DNA glycosylases. J. Mol. Biol., 318 (5), 1251-1264. Handa, P.⁺, Acharya, N.⁺, and Varshney, U. (2002) Effects of mutations at tyrosine 66 and asparagine 123 in the active site pocket of Escherichia coli uracil DNA glycosylase on uracil excision from synthetic DNA oligomers: evidence for the occurrence of long-range interactions between the enzyme and substrate. (+ joint first author) *Nucleic Acids Res, 30(14), 3086-3095. Handa, P., Acharya, N.,* Talwar R. K., Roy, S., and Varshney, U. (2002) Contrasting effects of mutating active site residues, aspartic acid 64 and histidine 187 of Escherichia coli uracil-DNA glycosylase on uracil excision and interaction with an inhibitor protein. Indian J. Biochem. Biophys., 29, 312-317. Saikrishnan, K., Jeyakanthan, Venkatesh, J., Acharya, N., Purnapatre, K., Sekar, K., Varshney, U. and Vijayan, M. (2002) Crystallization and preliminary X-ray studies on the single stranded DNA binding protein from Mycobacterium tuberculosis. *Acta* Crystallogr D Biol Crystallogr, 58, 327-329. Handa, P., Acharya, N. and Varshney, U. (2001) Chimeras between single stranded DNA binding proteins from Escherichia coli and Mycobacterium tuberculosis reveal that their C-terminal domains interact with uracil-DNA glycosylases. *J. Biol. Chem. 276, 16992-16997. Handa, P., Acharya, N.,* Thanedar, S., Purnapatre, K. and Varshney, U. (2000) Distinct properties of single stranded DNA binding protein from Mycobacterium tuberculosis and its functional characterization in Escherichia coli. *Nucleic Acids Res. 28, 3823-3829. Sadhale, P., Sharma, N., Beena, P, Katoch, A., Acharya, N., and Singh, S. K. (1998) Modulation of polymerase II composition: a possible mode of transcriptional regulation of stress response in eukaryotes. J. Biosci.* 23, 331-335. Pre-prints Swagata Bose, Satya Ranjan Sahu, Abinash Dutta, Narottam Acharya (2023) A chemically-induced attenuated strain of Candida albicans generates robust protective immune responses and prevents systemic candidiasis development. bioRxiv 2023.11.03.565495; doi: https://doi.org/10.1101/2023.11.03.565495 Doureradjou Peroumal, Satya Ranjan Sahu, Premlata Kumari, Bhabasha Utkalaja, Narottam Acharya (2022) Commensal fungi Candida albicans modulates dietary high-fat induced alterations in metabolism, immunity, and gut microbiota. bioRxiv 2022.03.23.485455; doi: https://doi.org/10.1101/2022.03.23.485455. Prashant Khandagale, Shweta Thakur, Narottam Acharya (2020) Identification of PCNA interacting protein motifs in human DNA polymerase delta. bioRxiv 2020.02.29.971473; doi: https://doi.org/10.1101/2020.02.29.971473. Prashant Khandagale, Doureradjou Peroumal, Kodavati Manohar, Narottam Acharya (2019) Human DNA polymerase delta is a pentameric holoenzyme with dimeric p12 subunit: Implications in enzyme architecture and PCNA interaction. bioRxiv 525485; doi: https://doi.org/10.1101/525485. Book chapter Narottam Acharya*, Kodavati Manohar, Shreenath Nayak, Avishek Chatterjee and Amrita Dalei (2106) DNA Polymerase: A putative drug target against Candidiasis. Frontiers in Life Sciences, Excel Indian Publishers, New Delhi, India. Pp. 12-23

Details

Genomic Instability and Diseases

Peer reviewed publications:

Jugal Kishor Sahu, Shweta Thakur, Ipsita Subhadarsini, and Narottam Acharya (2024) p12 isoform-2 is a regulatory subunit of human DNA polymerase delta and is dysregulated in various cancers. FEBS Letters, doi.org/10.1002/1873-3468.15070.
Bhabasha Gyanadeep Utkalaja, Shraddheya Kumar Patel, Satya Ranjan Sahu, Abinash Dutta, and Narottam Acharya (2024) Critical roles of Dpb3-Dpb4 sub-complex of DNA polymerase epsilon in DNA replication, genome stability, and pathogenesis of Candida albicans. mBio. doi.org/10.1128/mbio.01227-24.
Satya Ranjan Sahu, Abinash Dutta, Doureradjou Peroumal, Premlata Kumari, Bhabasha Gyanadeep Utkalaja, Shraddheya Kumar Patel, and Narottam Acharya (2024) Immunogenicity and efficacy of CNA25 as a potential whole-cell vaccine against systemic candidiasis. EMBO Molecular Medicine.doi: 10.1038/s44321-024-00080-8.
Bhabasha Gyanadeep Utkalaja, Satya Ranjan Sahu, Sushree Subhashree Parida, and Narottam Acharya (2024) Hsp90-mediated multi-drug resistance in DNA polymerase defective strains of Candida albicans. Journal of Fungi, 10, 222. https://doi.org/10.3390/jof10030222.
Swagata Bose, Satya Ranjan Sahu, Abinash Dutta, and Narottam Acharya (2024) A chemically-induced attenuated strain of Candida albicans generates robust protective immune responses and prevents systemic candidiasis development. eLife, 13:RP93760. doi: 10.7554/eLife.93760.
Satya Ranjan Sahu, Bhabasha Gyanadeep Utkalaja, Shraddheya Kumar Patel, and Narottam Acharya (2023) Spot Assay and Colony Forming Unit (CFU) Analyses-based sensitivity test for Candida albicans and Saccharomyces cerevisiae. Bio-protocol, 13(21):e4872. doi: 10.21769/BioProtoc.4872.
Satya Ranjan Sahu, Shweta Thakur, Doureradjou Peroumal, Bhabasha Gyanadeep Utkalaja, Abinash Dutta, Premlata Kumari, Ipsita Subhadarsini, and Narottam Acharya (2023) 4-Nitroquinoline 1-oxide induces immune-cells death to onset early immunosuppression during Oral squamous cell carcinoma development. Frontiers in Immunology, 14:1274519. doi: 10.3389/fimmu.2023.1274519.
Shraddheya Kumar Patel, Satya Ranjan Sahu, and Narottam Acharya (2023) Cell cycle Analysis of Candida albicans by Flow Cytometry. Bio-protocol, 13(20): e4748. DOI: 10.21769/BioProtoc.4748.
Premlata Kumari, Satya Ranjan Sahu, Abinash Dutta, Bhabasha Gyanadeep Utkalaja, and Narottam Acharya (2023) RAD51-WSS1 dependent genetic pathways are essential for DNA-Protein crosslink repair and pathogenesis in Candida albicans. Journal of Biological Chemistry, doi.org/10.1016/j.jbc.2023.104728. (On the cover page)
Swagata Bose, Durg Vijai Singh, Tapan Kumar Adhya, and Narottam Acharya (2023) Escherichia coli, but Not Staphylococcus aureus, Functions as a Chelating Agent That Exhibits Antifungal Activity against the Pathogenic Yeast Candida albicans. Journal of Fungi, 9, 286. https://doi.org/10.3390/jof9030286
Shraddheya Kumar Patel, Satya Ranjan Sahu, Bhabasha Gyanadeep Utkalaja, Swagata Bose, and Narottam Acharya (2023) Pol32, an accessory subunit of DNA polymerase delta, plays an essential role in genome stability and pathogenesis of Candida albicans. Gut microbes, DOI: 10.1080/19490976.2022.2163840.
Narottam Acharya, Louise Prakash, and Satya Prakash (2023) Yeast 9-1-1 complex acts as a sliding clamp for DNA synthesis by DNA polymerase ε. Journal of Biological Chemistry, Jan;299(1):102727. doi: 10.1016/j.jbc.2022.102727.
Doureradjou Peroumal, Satya Ranjan Sahu, Premlata Kumari, Bhabasha G. Utkalaja, and Narottam Acharya (2022) Commensal Fungus Candida albicans Maintains a Long-Term Mutualistic Relationship with the Host To Modulate Gut Microbiota and Metabolism. Microbiology Spectrum, DOI: 10.1128/spectrum.02462-22.
Satya Ranjan Sahu, Swagata Bose, Manish Singh, Premlata Kumari, Abinash Dutta, Bhabasha G. Utkalaja, Shraddheya Kumar Patel, and Narottam Acharya (2022) Vaccines against Candidiasis: Status, Challenges and Emerging opportunity. Front. Cell. Infect. Microbiol., DOI: 10.3389/fcimb.2022.1002406.
Kodavati Manohar, Prashant Khandagale, Shraddheya Kumar Patel, Jugal Kishor Sahu, and Narottam Acharya (2021) Ubiquitin-binding domain of DNA polymerase eta lacking the PCNA-interacting-protein motif directly binds to PCNA and regulates translesion DNA synthesis. Journal of Biological Chemistry, Dec 18;298(2):101506. doi: 10.1016/j.jbc.2021.101506.
Premlata Kumari, Rajivgandhi Sundaram, Kodavati Manohar, Dileep Vasudevan and Narottam Acharya (2021) Interdomain connecting loop and J loop structures determine cross-species compatibility of PCNA. Journal of Biological Chemistry, Jul;297(1):100911. doi: 10.1016/j.jbc.2021.100911.
Rajivgandhi Sundaram, Kodavati Manohar, Shraddheya Kumar Patel, Narottam Acharya and Dileep Vasudevan (2021) Structural analyses of PCNA from the fungal pathogen Candida albicans. FEBS Letters, May;595(9):1328-1349. doi: 10.1002/1873-3468.
Narottam Acharya, Shraddheya Kumar Patel, Satya Ranjan Sahu, and Premlata Kumari (2020) “PIPs” in DNA polymerase – PCNA interaction affairs. Biochem. Soci. Trans. Nov 16:BST20200678. doi: 10.1042/BST20200678.
Swagata Bose, Shifu Aggarwal, DurgVijai Singh and Narottam Acharya (2020) Extracellular vesicles: An emerging platform in gram-positive bacteria. Micro. cell Vol. 7, No. 12, pp. 312 – 322; doi: 10.15698/mic2020.12.737.
Prashant Khandagale, Shweta Thakur and Narottam Acharya (2020) Identification of PCNA interacting protein motifs in human DNA polymerase delta, Bioscience Reports, 40 (4). (doi.org/10.1042/BSR20200602)
Narottam Acharya, Prashant Khandagale, Shweta Thakur, Jugal Kishor Sahu and Bhabasha Gyanadeep Utakalaja (2020) Quaternary structural diversity in Eukaryotic DNA Polymerases: Monomeric to Multimeric form. Current Genetics, Aug; 66 (4):635-655. doi: 10.1007/s00294-020-01071-1.
Doureradjou Peroumal, Kodavati Manohar, Shraddheya Kumar Patel, Premlata Kumari, Satya Ranjan Sahu and Narottam Acharya (2019) Virulence and pathogenicity of a Candida albicans mutant with reduced filamentation. Cellular Microbiology, 21 (12) (doi.org/10.1111/cmi.13103).
Prashant Khandagale, Doureradjou Peroumal, Kodavati Manohar and Narottam Acharya (2019) Human DNA polymerase delta is a pentameric holoenzyme with a dimeric p12 subunit. Life Science Alliance, Vol. 2, No., 2. (doi.org/10.26508/lsa.201900323)
Narottam Acharya, Kodavati Manohar, D. Peroumal, Prashant Khandagale, Shraddheya Kumar Patel, Satya Ranjan Sahu, and Premlata Kumari (2019) Multifaceted activities of DNA Polymerase eta: Beyond translesion DNA synthesis. Curr. Genetics, 65(3), 649-656. (doi.org/10.1007/s00294-018-0918-5).
Jingde, N., Ray, R., Sinha, S., Rana, K., Singh, S. K., Khandagale, P., Narottam Acharya and V. Rai (2018) Cysteine mediated disulfide bond formation in RAGE V domain facilitates its functionally relevant dimerization. Biochimie, 154, 55-61.
Kodavati Manohar, Doureradjou Peroumal and Narottam Acharya (2018) TLS dependent and independent functions of DNA polymerase eta (Polh/ Rad30) from Pathogenic Yeast Candida albicans. Molecular Microbiology, 110 (5), 707-727
Suresh Satpati, Kodavati Manohar, Narottam Acharya*, Anshuman Dixit. (2017) Comparative molecular dynamics studies of heterozygous open reading frames of DNA polymerase eta (η) in pathogenic yeast Candida albicans. Sci Rep., 7:41087. doi: 10.1038/srep41087. (Joined corresponding author)
Kodavati Manohar and Narottam Acharya (2015) Characterization of Proliferating Cell Nuclear Antigen (PCNA) from Pathogenic Yeast Candida albicans and its functional analyses in S. cerevisiae. BMC-Microbiology, 15:257.
Yoon J.H⁺., Acharya N⁺., Jeseong P., Debashree Basu, Prakash S. and Prakash L. (2014) Identification of two functional PCNA binding domains in human DNA polymerase κ (+ joint first author). Genes to Cells., 19(7):594-601.
Acharya N., Kalssen R., Johnson R.E., Prakash L. and Prakash S. (2011) PCNA binding domains in all three subunits of yeast DNA polymerase δ modulate its function in DNA replication. Proc Natl Acad Sci USA., Nov.1; 108(44):17927-17932.
Acharya N⁺., Yoon J.H⁺., Hutwitz J., Prakash L. and Prakash S. (2010) DNA polymerase eta lacking the ubiquitin-binding domain promotes replicative lesion bypass in human cells (⁺ joint first author). Proc Natl Acad Sci USA., Jun 8; 107(23):10401-10405.
Acharya N., Johnson R.E., Pagès V., Prakash L. and Prakash S. (2009) Yeast Rev1 protein promotes complex formation of DNA polymerase zeta with Pol32 subunit of DNA polymerase delta. Proc Natl Acad Sci USA., Jun 16; 106(24):9631-9636.
Acharya N., Yoon J.H., Gali H., Unk I., Haracska L., Johnson R.E., Hutwitz J., Prakash L. and Prakash S. (2008) Roles of PCNA-binding and ubiquitin-binding domains in human DNA polymerase eta in translesion DNA synthesis. Proc Natl Acad Sci USA., Nov 18; 105 (46):17724-17729.
Pagès V., Bresson A., Acharya N., Prakash L. Fuchs R.P. and Prakash S. (2008) Requirement of Rad5 for DNA polymerase zeta-dependent translesion synthesis in Saccharomyces cerevisiae. Genetics, 2008 Sep; 180(1):73-82.
Acharya N., Haracska L., Prakash S. and Prakash L. (2007) Complex formation of yeast Rev1 with DNA polymerase {eta}. Mol Cell Biol., Dec; 27 (23):8401-8408.
Acharya N., Brahma A., Haracska L., Prakash S. and Prakash L. (2007) Mutations in the Ubiquitin Binding UBZ Motif of DNA Polymerase {eta} Do Not Impair Its Function in Translesion Synthesis during Replication. Mol Cell Biol., Oct; 27(20):7266-7272.
Acharya N., Johnson R.E., Prakash S. and Prakash L. (2006) Complex formation with Rev1 enhances the proficiency of Saccharomyces cerevisiae DNA polymerase zeta for mismatch extension and for extension opposite from DNA lesions. Mol. Cell Biol., Dec. 26 (24), 9555-9563.
Acharya N., Haracska L., Johnson R.E., Unk I., Prakash S. and Prakash L. (2005) Complex formation of yeast Rev1 and Rev7 proteins: a novel role for the polymerase-associated domain. Mol. Cell Biol., Nov. 25 (21), 9734-9740.
Haracska L., Acharya N., Unk I., Johnson R.E., Hurwitz J., Prakash L. and Prakash S. (2005) A single domain in human DNA polymerase iota mediates interaction with PCNA: implications for translesion DNA synthesis. Mol. Cell Biol., Feb. 25 (3), 1183-1190
Acharya N, Talawar R. K., Purnapatre K, Varshney U. (2004) Use of sequence microdivergence in mycobacterial ortholog to analyze contributions of the water-activating loop histidine of Escherichia coli uracil-DNA glycosylase in reactant binding and catalysis. Biochem. Biophys. Res. Commun., 320(3), 893-899.
Acharya, N., Talawar R. K., Saikrishnan, K., Vijayan, M and Varshney, U. (2003) Substitutions at tyrosine 66 of Escherichia coli uracil DNA glycosylase lead to characterization of an efficient enzyme that is recalcitrant to product inhibition. Nucleic Acids Res., 31(24), 7216-7226.
Acharya, N., Kumar P. and Varshney, U. (2003) Complexes of Uracil-DNA glycosylase inhibitor protein, Ugi, with Mycobacterium smegmatis and Mycobacterium tuberculosis uracil-DNA glycosylases. Microbiology 149, 1647-1658.
Saikrishnan, K., Jeyakanthan, Venkatesh, J., Acharya, N., Purnapatre, K., Sekar, K., Varshney, U. and Vijayan, M. (2003) Structure of Mycobacterium tuberculosis single stranded DNA binding protein. Variability in quaternary structure and its implications. J. Mol. Biol., 331, 385-393.
Acharya, N., Roy, S., and Varshney, U. (2002) Mutational analysis of the uracil DNA glycosylase inhibitor protein and its interaction with Escherichia coli uracil DNA glycosylase. J. Mol. Biol., 321 (4), 579-590.
Acharya, N., and Varshney, U. (2002) Biochemical properties of single stranded DNA binding protein from Mycobacterium smegmatis, a fast growing mycobacterium and its physical and functional interaction with uracil DNA glycosylases. J. Mol. Biol., 318 (5), 1251-1264.
Handa, P.⁺, Acharya, N.⁺, and Varshney, U. (2002) Effects of mutations at tyrosine 66 and asparagine 123 in the active site pocket of Escherichia coli uracil DNA glycosylase on uracil excision from synthetic DNA oligomers: evidence for the occurrence of long-range interactions between the enzyme and substrate. (+ joint first author) Nucleic Acids Res, 30(14), 3086-3095.
Handa, P., Acharya, N., Talwar R. K., Roy, S., and Varshney, U. (2002) Contrasting effects of mutating active site residues, aspartic acid 64 and histidine 187 of Escherichia coli uracil-DNA glycosylase on uracil excision and interaction with an inhibitor protein. Indian J. Biochem. Biophys., 29, 312-317.
Saikrishnan, K., Jeyakanthan, Venkatesh, J., Acharya, N., Purnapatre, K., Sekar, K., Varshney, U. and Vijayan, M. (2002) Crystallization and preliminary X-ray studies on the single stranded DNA binding protein from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr, 58, 327-329.
Handa, P., Acharya, N. and Varshney, U. (2001) Chimeras between single stranded DNA binding proteins from Escherichia coli and Mycobacterium tuberculosis reveal that their C-terminal domains interact with uracil-DNA glycosylases. J. Biol. Chem. 276, 16992-16997.
Handa, P., Acharya, N., Thanedar, S., Purnapatre, K. and Varshney, U. (2000) Distinct properties of single stranded DNA binding protein from Mycobacterium tuberculosis and its functional characterization in Escherichia coli. Nucleic Acids Res. 28, 3823-3829.
Sadhale, P., Sharma, N., Beena, P, Katoch, A., Acharya, N., and Singh, S. K. (1998) Modulation of polymerase II composition: a possible mode of transcriptional regulation of stress response in eukaryotes. J. Biosci. 23, 331-335.

Pre-prints

Swagata Bose, Satya Ranjan Sahu, Abinash Dutta, Narottam Acharya (2023) A chemically-induced attenuated strain of Candida albicans generates robust protective immune responses and prevents systemic candidiasis development. bioRxiv 2023.11.03.565495; doi: https://doi.org/10.1101/2023.11.03.565495
Doureradjou Peroumal, Satya Ranjan Sahu, Premlata Kumari, Bhabasha Utkalaja, Narottam Acharya (2022) Commensal fungi Candida albicans modulates dietary high-fat induced alterations in metabolism, immunity, and gut microbiota. bioRxiv 2022.03.23.485455; doi: https://doi.org/10.1101/2022.03.23.485455.
Prashant Khandagale, Shweta Thakur, Narottam Acharya (2020) Identification of PCNA interacting protein motifs in human DNA polymerase delta. bioRxiv 2020.02.29.971473; doi: https://doi.org/10.1101/2020.02.29.971473.
Prashant Khandagale, Doureradjou Peroumal, Kodavati Manohar, Narottam Acharya (2019) Human DNA polymerase delta is a pentameric holoenzyme with dimeric p12 subunit: Implications in enzyme architecture and PCNA interaction. bioRxiv 525485; doi: https://doi.org/10.1101/525485.

Book chapter

Narottam Acharya*, Kodavati Manohar, Shreenath Nayak, Avishek Chatterjee and Amrita Dalei (2106) DNA Polymerase: A putative drug target against Candidiasis. Frontiers in Life Sciences, Excel Indian Publishers, New Delhi, India. Pp. 12-23

Group

Details

Laboratory of Genomic Instability and Diseases

Ph.D. students:

	Jugal Kishore Sahu (CSIR-SRF): Role of POLD4 of human DNA polymerase delta in genome stability and carcinogenesis (Thesis submitted)
	Ipsita Subhadarsini (CSIR- SRF): TLS DNA Polymerases and Chemo-resistance
	Sushree Subhashree Parida (DBT-SRF): Cell fate without TLS DNA Polymerase
	Rakseh Padhan (UGC-SRF): Connecting protein translation with DNA replication
	Samanwita Das (UGC-SRF): t-RNA modification enzymes and fungal pathogenesis
	Supriti Roy (DBT-JRF): Fungal-host interaction and pan-fungal vaccine development Arunima Pramanick (DBT-JRF): Nucleotide Mtabolism in fungal pathogens

Lab. Technician:

Mr. Sitendra Prasad Panda

Our Graduates:

	Dr. Kodavati Manohar, Ph. D. (Graduated from the Laboratory in the year 2018) Thesis entitled “*Characterization of DNA polymerase eta (Polη/Rad30) from pathogenic yeast Candida albicans: Role in genome stability, morphogenesis and multidrug resistance*” ( Currently Pursuing Post-doctoral training at Houston Methodist, USA)
	Dr. Prashant R. Khandagale, Ph. D. (Graduated from the Laboratory in the year 2019) Thesis entitled “Targeting of human DNA polymerase delta to the replication machinery”. (Currently Pursuing Post-doctoral training at NIH)
	Dr. Premlata Kumari, Ph.D. (Graduated from the Laboratory in the year 2022) Thesis entitled “DNA-protein crosslink repair in pathogenic yeast Candida albicans” (Currently Asst. Prof. Women’s college, Patna)
	Dr. Shraddheya Kumar Patel, Ph.D. (Graduated from the Laboratory in the year 2022) Thesis entitled “Deciphering the role of Pol32, the non-essential subunit of DNA polymerase delta in Candida albicans pathogenesis” (Currently Pursuing Post-doctoral training at NIH)

Dr. Swagata Bose, Ph.D. ( Graduated from the Laboratory in the year 2023) Thesis entitled “Poly-microbial interaction regulating commensalism and pathogenicity of Candida albicans“. (Currently Pursuing Post-doctoral training at Institute of Maryland,USA)

Dr. Satya Ranjan Sahu, Ph.D. (Graduated from the Laboratory in the year 2023) Thesis entitled ” Role of DNA polymerases in the pathogenesis of Candida albicans: A step towards live attenuated whole cell vaccine development” (Currently Pursuing Post-doctoral training at University of Massachusetts, USA)

Dr. Bhabasha Gyanadeep Utkalaja (Graduated from the laboratory in the year 2024) Thesis entitled ”Deciphering the role of the non-essential subunits of DNA polymerase epsilon in Candida albicans pathogenesis ”

Our Alumni

Dr. Abinash Dutta, Ph.D. (DBT Project RA- from 2021-Sept. 2024)

Dr. Shweta Thakur, Ph.D. (NPDF/DBT-RA- from April 2018- March 2024)

Dr. Manish Singh, Ph.D. (DBT Project RA- 2021 (April-Nov.)

Dr. Doureradjou Peroumal, Ph. D. (CSIR/DBT-RA- 2016-March 2021)

Dr. Shreenath Nayak, Ph.D. (DBT-RA; from the year 2013-2016)

Dr. Jawed Alam, Ph.D. (CSIR-RA-2015-16)

Amrita Dalei (Lab. Technician – 2013-2018)