RecQ helicases are ubiquitious proteins required for maintenance of genome stability. In human, five RecQ family helicases have been identified of which, three are associated with genetic disorders like Bloom’s Syndrome, Werner’s syndrome and Rothmund-Thompson syndrome. Out of the five RecQ family helicases, the BLM, WRN and RecQ4 have been extensively studied with respect to DNA binding and unwinding activities. Among the five members of this helicase family, RecQ1 is the least explored helicase in terms of DNA binding and conformational changes associated with DNA recognition and unwinding. RecQ1 is known to unwind variety of substrates like Holliday junctions, forked duplexes and G-quadruplex DNA. Although RecQ1 has not been shown to be associated with any disease, the helicase has vital role in DNA repair and maintaining genome integrity. RecQ1 is the smallest and the most abundant RecQ helicase (72kDa). Diverse studies show that defects in or depletion of RecQ1 impairs cell growth, causes genome instability or induces mitotic catastrophe. RecQ1 is proposed to have a unique role in replication origin firing and nascent DNA synthesis and is critical for replication fork restart. Recently RecQ1 has gained attention due to its role in restoration of stalled replication forks upon DNA damage in association with other DNA repair proteins like PARP1.
Our group at IIT Kharagpur is mainly interested in structural and functional characterization of human RecQ1 and understanding the mechanism of unwinding and substrate specificity of human RecQ1 using fluorescence spectroscopic techniques. We are also studying the interactions of human RecQ1 with cellular protein partners that modulate its activity.
Apart from human RecQ1 we are also trying to functionally characterize the RecQ helicases from human parasite L.donovani, so as to understand the active DNA repair processes in the parasite that involves RecQ helicases.
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The catalytic core of Leishmania donovani RECQ helicase unwinds a wide spectrum of DNA substrates and is stimulated by replication protein A. Shikha K., Bharath G. S., Mukhopadhyay S. , Chakraborty M. , Ghosh S. , Khatun S. , De D. , Gupta A. N., Ganguly A. By The FEBS Journal 289 394-416 (2022)
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'LeishMan' topoisomerase I: an ideal chimera for unraveling the role of the small subunit of unusual bi-subunit topoisomerase I from Leishmania donovani Ganguly A, Das BB, Sen N, Roy A, Dasgupta SB and Majumder HK By Nucleic Acids Res 34 6286-97 (2006)
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Residues at the interface between zinc binding and winged helix domains of human RECQ1 play a significant role in DNA strand annealing activity. Mukhopadhyay S., Das T. , Bose M. , Jain C. K., Chakraborty M. , Mukherjee S. , Shikha K. , Das A. K., Ganguly A. By Nucleic Acids Research 49 11834-11854 (2021)
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Human RecQ helicases in transcription-associated stress management: bridging the gap between DNA and RNA metabolism Das T., Pal S. , Ganguly A. By Biological Chemistry 402 617-636 (2021)
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RecQ family helicases in replication fork remodelling and repair: Opening new avenues towards identification of potential targets for cancer chemotherapy Jain C., Mukhopadhyay S. , Ganguly A. By Anticancer Agents in Medicinal Chemistry - (2020)
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Crystal structures of Thermotoga maritima reverse gyrase: inferences for the mechanism of positive DNA supercoiling Rudolph MG, Del Toro Duany Y, Jungblut SP, Ganguly A, Klostermeier D By Nucleic Acids Res 41 1058-70 (2013)
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Reverse Gyrase Transiently Unwinds Double-Stranded DNA in an ATP-Dependent Reaction Ganguly A, Del Toro Duany Y, Klostermeier D By J Mol Biol. 425 32-40 (2013)
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ATP independent type IB topoisomerase of Leishmania donovani is stimulated by ATP: an insight into the functional mechanism Sengupta S, Ganguly A, Roy A, Bosedasgupta S, D'Annessa I, Desideri A and Majumder HK By Nucleic Acids Res 39 3295-3309 (2011)
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The latch modulates nucleotide and DNA binding to the helicase-like domain of Thermotoga maritime reverse gyrase and is required for positive DNA supercoiling Ganguly A, Del Toro Duany Y, Rudolph MG and Klostermeier D By Nucleic Acids Res. 39 1789-800 (2011)
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Betulinic acid, a catalytic inhibitor of topoisomerase I inhibits ROS mediated apoptotic topo I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death Ganguly A., Das BB., Roy A., Sen N., BoseDasgupta S., Mukhopadhayay S. and Majumder HK By Cancer Res 67 11848-58 (2007)
Principal Investigator
- Towards understanding the role of Winged Helix domain conformation in substrate selectivity, DNA binding and strand annealing activity of human RECQ1 Science and Engineering Research Board (SERB)
Ph. D. Students
Ayan Chatterjee
Area of Research: RecQ helicase from Leishmania donovani
Mayukh Chakraborty
Area of Research: RecQ1 interaction with replication protein A
Sourav Misra
Area of Research: Mechanistic studies of human RECQ1
Surasree Pal
Area of Research: Modulation of RecQ activity by replication protein A
Susmita Ghosh
Area of Research: DNA repair in Leishmania parasites
Tulika Das
Area of Research: Molecular Biology and Biophysics
