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News update:

  • Prof. Benu Brata Das has been elected as a Fellow of the National Academy of Sciences (FNASc), 2020

  • Prof. Benu Brata Das is selected for the Indian Council of Medical Research (ICMR) Prem Nath Wahi Award (Basic and Clinical Oncology), 2020

  • Prof. Benu Brata Das is selected for the S. Ramachandran- National Bioscience Awards for Career Development award 2019-2020, Department of Biotechnology, Government of India.

  • Elected member of Guha Research Conference from the year 2019.

  • Elected Fellow of West Bengal Academy of Science & Technology (WAST), 2019.


Key Research activity:

1. DNA Topoisomerase structure, cellular and biochemical functions. 

2. Explore the molecular mechanisms of DNA damage induced by covalent trapping of Top1 on DNA (Top1cc) and Tyrosyl-DNA phosphodiesterase 1 (TDP1) mediated DNA repair.

3. Explore new DNA repair pathways in mitochondria and the role of mtDNA damage in human diseases.

4.  Explore the role of post-translational modifications (PTMs i.e. phosphorylation, acetylation, methylation, ubiquitylation and SUMOylation) of DNA repair proteins and response to anticancer agents.

5. Unravel the functional and biological coupling of Poly(ADP-ribose)polymerase (PARP1) with DNA repair pathways.

6. Explore the molecular mechanism of PARP inhibitors in cancer treatment.

7. Anticancer Drug Discovery: Targeting DNA Topoisomerase with small molecules inhibitors in human cancer. 

Google Scholar: https://scholar.google.co.in/citations?user=dwb_Lk4AAAAJ&hl=en&oi=ao

Wellcome Trust/ DBT India alliance webpage: https://www.indiaalliance.org/fellow/benu-brata-das

Research Interest:

Genomic instability leads to cancer, premature aging, neurodegeneration and several human diseases. Other than the nuclear genome, mitochondria also harbor the small, circular DNA (mtDNA) that is essential for life. Mitochondrial reactive oxygen species (ROS) is the source for the endogenous DNA damage.

            DNA-repair systems provide a critical defense mechanism against exogenous DNA-damaging agents, such as the human carcinogen, and endogenous sources such as ROS (reactive oxygen species) generated from normal cellular metabolism. This damage includes SSBs (single-strand breaks), DSBs (double-strand breaks) as well as chemical modifications of the bases and sugars. To avoid the deleterious consequences of damage accumulation, cells have developed DNA damage response (DDR) pathways. In recent years it has become apparent that the cellular DDR is a rich signaling network. In addition to DNA repair per se, this network activates cell cycle checkpoints and modulates numerous cellular processes while the damage is being repaired. DNA damage induces post-translational modifications (PTMs i.e. phosphorylation, acetylation, methylation, ubiquitylation and SUMOylation) of histones and non-histone proteins to coordinate chromatin organization and genome maintenance. 

            Our laboratory primarily focuses on DNA topoisomerases, Top1 is essential in higher eukaryotes as it relaxes positive DNA supercoiling in advance of replication forks and transcription complexes as well as negative supercoiling behind such complexes. DNA topoisomerase I (Top1) regulate DNA supercoiling both in the nucleus and mitochondria to enable faithful transmission of our genetic information to the offspring. However, Top1 are toxic when trapped on the DNA (Top1 cleavage complexes; Top1cc) in the presence of anticancer drug camptothecin or endogenous DNA damage generated by reactive oxygen species (ROS). A key repair enzyme for Top1cc is tyrosyl-DNA phosphodiesterase (TDP1), which hydrolyzes the phosphodiester bond between the DNA 3'-end and the Top1 tyrosyl moiety. Active site mutation of TDP1 causes the severe neurodegenerative syndrome spinocerebellar ataxia with axonal neuropathy (SCAN1). TDP1 repairs Top1cc by forming complexes with the DNA single stranded break repair enzymes like PARP1-XRCC1-PNKP-Polymerase beta-ligaseIII. Top1cc also generates DNA double-strand breaks, and induces phosphorylated TDP1, H2AX and Chk2 nuclear foci by activation of ATM. Therefore, Top1cc-induced DNA damage response is a complex signaling network and is not fully understood. To unravel the complexity of this signaling network in mechanistic detail and to identify new regulators and novel post-translational modifications of proteins essential for genome maintenance. We will also explore the potential role of mitochondrial DNA (mtDNA) damage, dynamics and metabolism in the pathological-etiology of SCAN1 and related genetic disorders. Thus, our group at IACS is focused to understand how new genes and novel post-translational modifications coordinate the DSBs repair signaling in cells, which can eventually pave the pathway into therapeutic benefit.

            We will address our questions using cutting-edge tools of molecular and cellular biology with special emphasis on live-cell microscopy followed by photo bleaching (FRAP assays), gene knockdown using RNAi technology, DNA damage evaluation in single cell by gamma-H2AX staining and Comet assays.

Nucleic Acids Res. 2016, 44(17):8363-75.

Our recent papers:

Interplay between symmetric arginine dimethylation and ubiquitylation regulates TDP1 proteostasis Q9 for the repair of topoisomerase I-DNA adducts

Bhattacharjee and Rehman et al., Cell Reports, 2022 (In press)

 

TDP1 knockout Leishmania donovani accumulate Topoisomerase 1-linked DNA damage and are hypersensitive to clinically used antileishmanial drugs

The FASEB Journal, 2022, 36(4): e22265 

 

Top1-PARP1 association and beyond: from DNA topology to break repair

PARP1 and PARP trapping with PARP inhibitors.  

NAR Cancer, 2021 Mar; 3(1): zcab003.

 

 Invited Presentations:

37. Invited lecture at  CSIR – Central Drug Research Institute, Lucknow on Feb 19, 2020. Title of the Talk:  Title: New regulators of DNA Topoisomerase 1-induced DNA damage and Repair.

36. Invited lecture at the international meeting EMSI202 organised by CSIR-IITR, Lucknow between Feb 18-20, 2020. Title of the Talk:  "Mitochondrial DNA damage promotes the etiology of neurodegenerative syndrome SCAN1"

35: Invited Lecture at the international meeting ICAL 2020 International Conference on Autophagy and Lysosomes, IISC-Bangalore, Bangalore. 16-18 January 2020.  Title of the Talk: SCAN1-TDP1 trapping on mitochondrial DNA promotes mitochondrial dysfunction and mitophagy.

34. Invited Lecture at ATW2019 meeting, 18TH ANNUAL INTERNATIONAL ATAXIA-TELANGIECTASIA WORKSHOP TAKING A MULTIDISCIPLINARY APPROACH. Houston Methodist Research Institute, Texas Medical Centre, Houston, USA between 1st to 4th of May 2019. Title: New regulators of DNA Topoisomerase1-induced DNA damage and Repair.

33. Invited Lecture at Wellcome Trust Cell Biology Centre, University of Edinburgh, Scotland, UK dated 25th April 2019. Title: New regulators of DNA Topoisomerase 1-induced DNA damage and Repair.

32. Invited Lecture at Northern Institute of Cancer Research, Newcastle University, UK dated 23 rd April2019. Title: New regulators of DNA Topoisomerase 1-induced DNA damage and Repair. 

31. Invited lecture at the American Catholic University, Washington DC, USA, Department of Biological Sciences, September 10th, 2018. Title: New Challenges in personalised cancer Chemotherapy.

30. Invited Lecture at the Centre of Gene regulation in Health and Disease at Cleveland  State University (CSU), Cleveland, OH, USA  dated 28th August, 2018. Title: New regulators of DNA Topoisomerase 1-induced DNA damage and Repair.

29.Invited lecture at the DNA Topoisomerases in Biology and Medicine Gordon Research Conference July 29 - August 3, 2018, Mount Holyoke College, MA, USA, Title of the talk: “PRMT5-Mediated Arginine Methylation of TDP1 for the Repair of Topoisomerase I Covalent Complexes"

28. Invited lecture at Indo-Israel meeting organized by INSA India. Recent Advances in Molcular genetics, Feb 12-13; 2018 Title of Talk: New regulators of DNA Topoisomerase I-induced DNA damage and repair.

27. IABS 2018 at IACS Kolkata, 1-3 rd Feb 2018; Title of Talk: New regulators of DNA Topoisomerase I-induced DNA damage and repair

26. Frontiers in Modern Biology, IISER, Kolkata dated January 19-21, 2018; Title of the lecture: New regulators of DNA Topoisomerase I-induced DNA damage and repair

25. Invited lecture at the Department of Molecular Genetics, ERASMUS MC medical school, Rotterdam, NETHERLANDS, Sept 21, 2017. Title of Talk: Role of PARP inhibitors in combination with Top1 inhibitors in cancer

24.EMBO Topoisomerase meeting at Les Diablerets, Switzerland, September 17-20, 2017: Presentation Title: Role of PARP inhibitors in combination with Top1 inhibitors in cancer

23. International meeting: Chromosome Stability 2016, between 15 – 18 December, 2016 in Trivandrum, Kerala, India.  Invited lecture : New regulators of DNA Topoisomerase I-induced DNA damage and repair".http://conference.iisertvm.ac.in/chromosome_stability/index.php/pages/speakers

22. ISA visiting professor honorary lecture, Institute of Advances Sciences, University of Bologna, Scuola Superiore di Studi Umanistici, via Marsala 26, Bologna, Italy NOV 08, 2016, FROM 05:30 PM TO 07:30 PM, Title: Targeting DNA topoisomerase in cancer: why so fascinating?" http://www.isa.unibo.it/en/lectures/lecture-by-benu-brata-das

21. University of Bologna, Department of Pharmacia and Biotechnology, Italy. Invited lecture on 28/10/2016 DALLE 14:30 ALLE 16:30, Dove Aula 1, Via Belmeloro 6. Title of The talk: DNA TOPOISOMERASE IN LIFE AND DEATH: NEW therapeutic opportunities ARE ON THE HORIZONhttp://www.fabit.unibo.it/it/eventi/copy24_of_i-seminari-del-fabit-1

20: BITS-PILANI Conference on Gene and Genome Regulation (BCGGR-2016), BITS, PILANI, Rajasthan. 18th to 20th, February, 2016. Title of Talk: "DNA Topoisomerase in life and Death: New therapeutic opportunities are on the horizon".

19: BITS, Goa Conference: New Frontiers in Chemistry- from Fundamentals to Applications (NFCFA 2015) during Dec 18th-19th 2015 in Goa. Title of Talk: "DNA Topoisomerase in life and Death: New therapeutic opportunities are on the horizon".

18. EMBO Meeting and workshop: DNA topoisomerases, DNA topology and human health, 13th-17th September 2015, Les Diablerets, Switzerland. Presentation title: “Poly(ADP-ribose) polymers regulate DNA topoisomerase I (Top1) nuclear dynamics and camptothecin sensitivity in living cells”

17. National Symposium: " Molecules to system" at Presidency University, Kolkata, 29th-31st January, 2014.  Invited lecture: "Coupling PARP1 and TDP1 repair pathways: New therapeutic opportunities are on the horizon" .

16. Chromosome Instability 2014: JNCASR Bangalore, India, 14-18th December, 2014.  Invited lecture : "Coupling PARP1 and TDP1 repair pathways: New therapeutic opportunities are on the horizon".

15. Gordon Research Conference : DNA Topoisomerase in Biology and Medicine: 10-15 September, 2014 at Sunday River Resort in Newry ME United States.  Presentation title: Coupling of Poly(ADP-ribose) polymerase (PARP1) and Tyrosyl-DNA phosphodiesterase ( TDP1) for the repair of Topoisomerase I-induced DNA damage.

14. Gordon Research Conference : DNA, Damage, Mutation & Cancer: March 16-21st, 2014 at the Ventura Beach Marriott, Ventura, California. Presentation title: Coupling of Poly(ADP-ribose) polymerase (PARP1) and Tyrosyl-DNA phosphodiesterase ( TDP1) for the repair of Topoisomerase I-induced DNA damage.

13. UGC-DRS Sponsored National Seminar on “Bioprospecting of Natural Products” scheduled at the Department of Zoology, The University of Burdwan during December 05-06, 2013. Title of talk: DNA Topoisomerase in Life and Death.

12. Gordon Research Conference: A Delicate Balance: Cellular Mutation Pathways in Genetic Stability and Disease at Newport, RI, USA Sep, 2012 Title of talk: “PARP1 is a critical cofactor for TDP1 repair function”.

11. National Cancer Institute Outstanding Postdoctoral Fellow award talk. January 2012, Selected among top five finalists for outstanding fellow at NCI/NIH. Title: “Novel role of TDP1 in the repair of Nuclear and Mitochondrial DNA: Implications in human diseases”.

10. Cold Spring Harbor meeting: Eukaryotic DNA Replication & Genome Maintenance meeting Cold Spring Harbor, NY, USA, September 2011. Title: “Coupling of Poly(ADP-ribose) polymerase (PARP1) and Tyrosyl-DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I (Top1)-mediated DNA damage.

9. Indian Institute of Science Education and Research, Mohali. Title: Novel role of DNA repair enzyme Tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria, India. November 2011.

8. Indian Institute of Technology-Bombay. Department of Biotechnology; Title: Novel role of DNA repair enzyme Tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria, India. November 2011.

7. Indian Institute of Science Education and Research, Kolkata. Title: Novel role of DNA repair enzyme Tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria, India. November 2011.

6. The Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India. Title: Novel role of DNA repair enzyme Tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria. Mohanpur, Nodia, India. November 2011.

5. 8th Young Investigator meeting Boston October, 2011 at the Stata Auditorium, MIT, Cambridge, MA, USA. Title: “A Novel Nuclear and Mitochondrial DNA repair enzyme Tyrosyl-DNA phosphodiesterase (TDP1): Insights into Topoisomerase1-induced DNA Damage and Human diseases”

4. 11th Annual Fellows and Young Investigators Colloquium at Williamsburg Marriott hotel from February 25, 2011. Title: Role of Tyrosyl-DNA phosphodiesterase (TDP1) in mitochondrial DNA repair.

3. Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Department of Carcinogenesis, Biomarker and Epidimology. Washington DC 20057. Title: ATM and/or DNA-PK facilitates repair of Topoisomerase I-associated DNA breaks by Novel phosphorylation of TDP1 at Serine 81. October 22, 2009.

2. NDDO Honorary Lecture: ATM and/or DNA-PK facilitates repair of Topoisomerase I-associated DNA breaks by Novel phosphorylation of TDP1 at Serine 81. 8th International Symposium on Targeted Anticancer Therapies 2010, March 4-6. Washington DC, USA.

1. 8th Annual Fellows and Young Investigators Colloquium at Ocean City MD from March 3-5, 2008. Title: DNA Damage induces phosphorylation at Ser81 of the DNA repair enzyme Tyrosyl-DNA phosphodiesterase (TDP1): Exploring its implication in DNA repair.



Academic Profile



Group

Sayan Das

JRF-CSIR/NET
MSc-Zoology
TDP1-methylation
das.sayan2009@gmail.com
Soumyadip Paul

Research Associate (DBT-RA)
PhD (BoseInstitute)
Structure and Biological function of PARP1
soumyadip06@gmail.com
Banhi Chowdhury

JRF-UGC/NET
MSc (Neurobiology,CU)
PARP1structure
PARPinhibitors
chowdhurybanhi17@gmail.com
Ishita Rehman

SRF-IACS
MSc Microbiology
PRMT5 a novel regulator of Topoisomerase 1-DNA damage and Repair
pcir@iacs.res.in
Arijit Ghosh

SRF-Wellcome Trust/ IA project
MSc Microbiology
Mitochondrial dysfunction and human disease
pcag@iacs.res.in
Srijita Paulchowdhuri

SRF-UGC/NET
MSc Microbiology
DNA damage response in Cancer and the post-translation regulation of TDP1
pcspc@iacs.res.in
Sangheeta Bhattacharjee

SRF-CSIR/NET
MSc Zoology
Mitochondrial Metabolism and transcriptional regulation
pcsb4@iacs.res.in
Saini Basu

SRF-CSIR/NET
MSc Zoology
Arginine methylation and DNA repair proteins
bcsb8@iacs.res.in
Souvik Nandy

SRF-CSIR/NET
MSc in Molecular Biology and Chemical Sciences
Cross Talk between TDP1-PARP1 in DNA reapir
bcsn@iacs.res.in
Sarita Das

DST-SERB, Research Associate
PhD
COVID19project
18889.sarita@gmail.com
Arpan Bhattacharyya

UGC-JRF(NET)
MSc-Physiology
Mitochondria dysfunction and human Disease
arpanbhattacharyya10@gmail.com

 


Publications

Roy Chowdhury S., Das SK., Banerjee B., Paul Chowdhuri S., Majumder H.K., and Das, B.B*. TDP1 knockout Leishmania donovani accumulate Topoisomerase1-linked DNA damage and are hypersensitive to clinically used antileishmanial drugs. The FASEB Journal, 2022, 36(4): e22265.

 

Bhattacharjee S, Rehman I, Nandy S, Das, B.B*. Post-translational regulation of Tyrosyl-DNA phosphodiesterase (TDP1 and TDP2) for the repair of the trapped topoisomerase-DNA covalent complex. DNA Repair (Amst)2022 Mar; 111:103277.

 

Das B.B.*., Ghosh A., Bhattacharjee, S., Bhattachrya ATrapped topoisomerase-DNA covalent complexes in the mitochondria and their role in human diseases. Mitochondrion, 2021 Sep;60:234-24. 

 

Chowdhuri, S. P., and Das, B.B.* Top1-PARP1 association and beyond: from DNA topology to break repairNAR Cancer, 2021, 1;3(1):zcab003.

 

De, A., Bala, S., Saha S., Das,  K.S., Akhtar, S., Adhikary, A., Ghosh, A., Huang, G.Z., Chowdhuri, S.P., Das, B. B., Tong, M.L., Mondal, R. Lanthanide clusters of phenanthroline containing a pyridine-pyrazole based ligand: magnetism and cell imaging. Dalton Trans. 2021, 50(10):3593-3609. 

 

Biswas, S., Das, B., Alam, P., Ghatak, A., Ghorai, U.K., Ghosh, A., Das, B.B., Laskar, I.R., Acharya, S. Supramolecular Design Strategies for Color Tuning of Iridium(III) Complexes Using a Common Framework of Cyclometalating Ligands. J. Phys. Chem. C, 125: 4730−4742, 2021. 

 

Kundu, B., Sarkar, D., Chowdhuri, S. P., Pal, S., Ghosh, A.Das, S. K., Mukherjee, A., Bhattacharya, D., Das, B.B.* Talukdar, A.* 2020. Development of a metabolically stable topoisomerase I poison as anticancer agent. Eur J Med Chem.;202:112551.

 

Bej R, Ghosh A, Sarkar J,Das BB, Ghosh S. Thiol-Disulfide Exchange Reaction Promoted Highly Efficient Cellular Uptake of Pyridyl Disulfide Appended Nonionic Polymers. 2020; Chembiochem. 2020; 21(20):2921-2926. 

 

Gain, C., Malik, S., Bhattacharjee, S., Ghosh. A, Robertson, E.S, Das, B.B., Saha, A. Proteasomal inhibition triggers viral oncoprotein degradation via autophagy-lysosomal pathway. PLoS Pathog. 2020,16, e1008105 

https://pubmed.ncbi.nlm.nih.gov/32092124/

 

Ghosh, A., Bhattacharjee, S., Paul Chowdhuri, S., Mallick, A, Rehman, I., Basu, S., and Das, B.B*. SCAN1-TDP1 trapping on mitochondrial DNA promotes mitochondrial dysfunction and mitophagy. SCIENCE ADVANCES20195, eaax9778

https://pubmed.ncbi.nlm.nih.gov/31723605/

Highlighted: 

1.  Mitochondria kill themselves to protect neurons from an early death: Research Matters -(https://researchmatters.in/news/mitochondria-kill-themselves-protect-neurons-early-death

2. https://www.indiaalliance.org/news/403

 

Halder D, Saha S, Singh RK, Ghosh I, Mallick D, Dey SK, Ghosh A, Das BB, Ghosh S, Jana SS. (2019) Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells. Mol Biol Cell. 30(12):1463-1476.

 

Kundu B, Das SK, Paul Chowdhuri S, Pal S, Sarkar D, Ghosh A, Mukherjee A, Bhattacharya D, Das BB*, Talukdar A*. (2019) Discovery and Mechanistic Study of Tailor-Made Quinoline Derivatives as Topoisomerase 1 Poison with Potent Anticancer Activity. J Med Chem. 62(7):3428-3446.

https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01938

Highlight: The Hindu https://www.thehindu.com/sci-tech/science/kolkata-researchers-use-novel-compound-to-kill-cancer-cells/article27103775.ece

 

Rehman, I; Basu, S; Das, S.K.; Bhattacharjee, S; Ghosh, A; Pommier, Y*; Das BB*. (2018) PRMT5-mediated arginine methylation of TDP1 for the repair of topoisomerase I covalent complexes. Nucleic. Acids Research.46:5601-5617. 

https://academic.oup.com/nar/article/46/11/5601/4990012

HIGHLIGHTS: 

1. A new window to DNA repair mechanism and cancer therapy

https://www.indiaalliance.org/news/343

2. The regulation, functions and clinical relevance of arginine methylation.

Nature reviews. Molecular cell biology, 2019
 

Mallick A, Kuman MM, Ghosh A,‡ Das BB., ‡ and Basu S.Cerberus Nanoparticles: Co targeting of Mitochondrial DNA and Mitochondrial Topoisomerase I in Breast Cancer Cells. ACS Applied Nano Materials, 1 (5), 2195-2205, 2018.

 

S Bhowal, A Ghosh, SP Chowdhuri, R Mondal*, B.B. Das #*. (2018) A Novel Metallogel Based Approach to Synthesize (Mn, Cu) Doped ZnS Quantum Dots and Labelling of MCF-7 Cancer Cells. Dalton Transactions, 47, 6557.

 

Das SK, Ghosh A, Paul Chowdhuri S, Halder N, Rehman I, Sengupta S, Sahoo KC, Rath H*, Das BB # *. Neutral Porphyrin Derivative Exerts Anticancer Activity by Targeting Cellular Topoisomerase I (Top1) and Promotes Apoptotic Cell Death without Stabilizing Top1-DNA Cleavage Complexes. J. Med. Chem., 2018, 61 (3), pp 804–817

https://pubs.acs.org/doi/10.1021/acs.jmedchem.7b01297

Highlighted: The Hindu Newspaper : https://www.thehindu.com/sci-tech/science/a-novel-compound-to-kill-cancer-cells/article22436904.ece

 

Maji S, Alam P, Kumar GS, Biswas S, Sarkar PK, Das B, Rehman I, Das BB #, Jana NR, Laskar IR, Acharya S. Induced Aggregation of AIE-Active Mono-Cyclometalated Ir(III) Complex into Supramolecular Branched Wires for Light-Emitting Diodes.  Small. 2017 15, 1603780-1603787. 

 

Das, S.K., Rehman, I., Ghosh, A., Sengupta, S., Majumder, P., Jana, B and Das BB*#. Poly(ADP-ribose) polymers regulate DNA topoisomerase I (Top1) nuclear dynamics and camptothecin sensitivity in living cells. 2016, Nucleic. Acids Res. 44, 8363-75.

The article got highlighted in several leading Indian news media including :

Nature India: Combo therapy against drug-resistant cancers :

http://www.natureasia.com/en/nindia/article/10.1038/nindia.2016.127 

Times of India

http://timesofindia.indiatimes.com/city/kolkata/Combo-therapy-against-ovarian-breast-cancer-can-overcome-drug-resistance/articleshow/54518742.cms,

Wellcome Trust / DBT India Alliance:

http://www.wellcomedbt.org/news/105

 

Majumder, P., Bathula, C., Basu, S., Das, SK., Agarwal, R., Hati, S., Singh, A., Sen, S* and Das BB *#. (2015) Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity. European Journal of Medicinal Chemistry, 102:540-51. 

https://www.ncbi.nlm.nih.gov/pubmed/26312433

 

Pommier Y, Huang SY, Gao R, Das BB, Murai J, Marchand C. Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2). DNA Repair (Amst). 2014 Jul; 19:114-29. (Review)

https://www.ncbi.nlm.nih.gov/pubmed/24856239

 

Das BB *#, Huang S.N., Murai J., Rehman I., Amé J.-C., Sengupta S., Das S.K., Majumdar P., Zhang H., Biard D., Majumder H.K., Schreiber V., Pommier Y.*, PARP1-TDP1 coupling for the repair of topoisomerase I-induced DNA damage, Nucleic. Acids Res., 2014 Apr;42(7):4435-49. * Corresponding authors

https://www.ncbi.nlm.nih.gov/pubmed/24493735

Highlighted: 

1. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action; Science Translational Medicine  2016:

2. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nature Reviews Molecular Cell Biology 2017

volume (2017

 

Rui G¶., Das BB¶., Chatterjee R., Vinson C and Pommier Y., Epigenetic and genetic inactivation of tyrosyl-DNA-phosphodiesterase 1 (TDP1) in human lung cancer cells. DNA Repair, 2014 Jan; 13:1-9. ¶ Joint first author. 

 

Murai J., Huang SY., Das BB, Renaud A., Zhang Y., Doroshow JH., Ji J.,Takeda S and Pommier Y. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Research 72(21): 5588-99. (2012) https://www.ncbi.nlm.nih.gov/pubmed/23118055

 
Murai J., Huang SY., Das BB, Dexheimer TS., Takeda S and Pommier Y. Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damages induced by topoisomerases I and II, and base alkylation in vertebrate cells. J. Biol. Chem, 287(16):12848-57. (2012) https://www.ncbi.nlm.nih.gov/pubmed/22375014
 
Douarre C., Sourbier C., Dalla Rosa I., Das BB., Redon CE., Zhang H., Neckers L and Pommier Y. Mitochondrial Topoisomerase I is Critical for Mitochondrial Integrity and Cellular Energy Metabolism. PLoS One.;7(7):e41094. (2012)https://www.ncbi.nlm.nih.gov/pubmed/22911747
 
Das, BB, Dexheimer TS, Maddali K and Pommier Y. Role of Tyrosyl DNA Phosphodiesterase (TDP1) in mitochondria. Proc Natl Acad Sci U S A. 16;107(46):19790-19795. 2010. https://www.ncbi.nlm.nih.gov/pubmed/21041670
 
Das, BB, Antony S, Gupta, S, Dexheimer TS, Redon CE, Garfield S, Shiloh Y and Pommier Y. Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK. EMBO J. 28, 3667-3680. 2009. https://www.ncbi.nlm.nih.gov/pubmed/19851285
 
Sordet, O., Redon, C, Guirouilh-Barbat J., Smith S, Solier, S, Douarre, C, Conti, C, Nakamura, A, Das, BB, Nicolas E, Kohn, KW, Bonner, WM, Pommier, Y. Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks. EMBO Rep . 10(8):887-93. 2009. https://www.ncbi.nlm.nih.gov/pubmed/19557000
 
Das BB, Ganguly A, Majumder HK. DNA topoisomerases of Leishmania: the potential targets for anti-leishmanial therapy. Adv Exp Med Biol.; 625:103-15. Review. 2008.https://www.ncbi.nlm.nih.gov/pubmed/18365662
 
Roy A, Ganguly A, BoseDasgupta S, Das BB, Pal C, Jaisankar P, Majumder HK. Mitochondria-dependent reactive oxygen species-mediated programmed cell death induced by 3,3'-diindolylmethane through inhibition of F0F1-ATP synthase in unicellular protozoan parasite Leishmania donovani. Mol Pharmacol. , 74, 1292-307. 2008.https://www.ncbi.nlm.nih.gov/pubmed/18703668
 
BoseDasgupta S, Das BB, Sengupta S, Ganguly A, Roy A, Dey S, Tripathi G, Dinda B, Majumder HK. The caspase-independent algorithm of programmed cell death in Leishmania induced by baicalein: the role of LdEndoG, LdFEN-1 and LdTatD as a DNA 'degradesome'. Cell Death Differ, 10, 1629-40. 2008. https://www.ncbi.nlm.nih.gov/pubmed/18566607
 
Bosedasgupta S., Das BB. Ganguly A., Roy A., Majumder HK. Amino acids 39-456 of the large subunit and 210-262 of the small subunit constitute the minimal functionally interacting fragments of the unusual heterodimeric topoisomerase IB of Leishmania. Biochem J. 15; 481-9. 2008. https://www.ncbi.nlm.nih.gov/pubmed/17924857
 
Bosedasgupta S., Ganguly A., Das BB., Roy A., Majumder HK. The large subunit of Leishmania topoisomerase I functions as the 'molecular steer' in type IB topoisomerase. Molecular Microbiology. 67, 31-46. 2008. https://www.ncbi.nlm.nih.gov/pubmed/18036140
 
Roy A., Das BB., Ganguly A., Bosedasgupta S., Khalko NV., Pal C., Dey S., Giri VS. and Majumder HK An insight into the mechanism of inhibition of unusual bi-subunit topoisomerase I from Leishmania donovani by 3,3'-di-indolylmethane, a novel DNA topoisomerase I poison with a strong binding affinity to the enzyme. Biochem J. 409, 611-22. 2008. https://www.ncbi.nlm.nih.gov/pubmed/17924857
 
Ganguly A., Das BB., Roy A., Sen N., Dasgupta SB., Mukhopadyay S., Majumder HK., Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species-mediated apoptotic topoisomerase I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death. Cancer Res. 24: 11848-58. 2007. https://www.ncbi.nlm.nih.gov/pubmed/18089815
 
Das BB., Bosedasgupta S., Ganguly A., Majumder S., Roy A and Majumder HK Leishmania donovani bisubunit topoisomerase I gene fusion leads to an active enzyme with conserved type IB enzyme function. FEBS J. 274:150-63. 2007.https://www.ncbi.nlm.nih.gov/pubmed/17222179
 
Sen N., Banerjee B., Das BB., Ganguly A., Sen T., Pramanik S., Mukhopadhay S and Majumder HK Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex. Cell Death Differ. 2. 358-67. 2007.
 
Das BB., Sengupta T., Ganguly A. and Majumder HK., Topoisomerases of kinetoplastid parasites: why so fascinating? Molecular Microbiology. 62, 917-27. 2006. https://www.ncbi.nlm.nih.gov/pubmed/17042788
 
Sen N, Banerjee B, Gupta SS, Das BB, Ganguly A, Majumder HK. Leishmania donovani: dyskinetoplastid cells survive and proliferate in the presence of pyruvate and uridine but do not undergo apoptosis after treatment with camptothecin. Exp Parasitol. 115. 215-9. 2007. https://www.ncbi.nlm.nih.gov/pubmed/17027973
 
Ganguly A., Das BB., Sen N., Roy A., Dasgupta SB and Majumder HK. LeishMan' topoisomerase I: an ideal chimera for unraveling the role of the small subunit of unusual bi-subunit topoisomerase I from Leishmania donovani. Nucleic Acids Res. 34, 6286-97. 2006.https://www.ncbi.nlm.nih.gov/pubmed/17098934
 
Das BB, Sen N, Dasgupta SB, Ganguly A, Majumder HK. Differential induction of Leishmania donovani bi-subunit topoisomerase I-DNA cleavage complex by selected flavones and camptothecin: activity of flavones against camptothecin-resistant topoisomerase I. Nucleic Acids Res. 34, 1121-32. 2006.https://www.ncbi.nlm.nih.gov/pubmed/16488884
 
Sen N, Das BB, Ganguly A, Banerjee B, Sen T and Majumder HK. Leishmania donovani: intracellular ATP level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells. Exp Parasitol. 114(3):204-14. 2006.https://www.ncbi.nlm.nih.gov/pubmed/16707127
 
Das BB, Ganguly A, Majumder HK. Topoisomerase research of kinetoplasti parasite Leishmania, with special reference to development of therapeutics. Indian J Med Res. 123(3):221-32. Review. 2006. https://www.ncbi.nlm.nih.gov/pubmed/16778306
 
Gosh S, Bandyopadhyay S, Pal S, Das BB, Bhattacharya DK, Mandal C. Increased interferon gamma production by peripheral blood mononuclear cells in response to stimulation of overexpressed disease-specific 9-O-acetylated sialoglycoconjugates in children suffering from acute lymphoblastic leukaemia. Br J Haematol. 128, 35-41. 2005.
 
Das BB ., Sen N, Dasgupta SB, Ganguly A, Majumder HK. N-terminal region of the large subunit of Leishmania donovani bi-subunit topoisomerase I is involved in DNA relaxation and interaction with smaller subunit. J Biol Chem. 280, 16335-44. 2005. https://www.ncbi.nlm.nih.gov/pubmed/15711017
 
Sen N, Das BB, Ganguly A, Mukherjee T, Bandyopadhyay S, Majumder HK. Camptothecin-induced imbalance in intracellular cation homeostasis regulates programmed cell death in unicellular hemoflagellate Leishmania donovani. J Biol Chem. 279, 52366-75. 2004. https://www.ncbi.nlm.nih.gov/pubmed/15355995
 
Sen N, Das BB, Ganguly A, Mukherjee T, Tripathi G, Bandyopadhyay S, Rakshit S, Sen T, Majumder HK. Camptothecin induced mitochondrial dysfunction leading to programmed cell death in unicellular hemoflagellate Leishmania donovani. Cell Death Differ. 8, 924-36. 2004. https://www.ncbi.nlm.nih.gov/pubmed/15118764
 
Das BB., Sen N, Ganguly A, Majumder HK. Reconstitution and functional characterization of the unusual bi-subunit type I DNA topoisomerase from Leishmania donovani. FEBS Lett. 565, 81-8. 2004. https://www.ncbi.nlm.nih.gov/pubmed/15135057
 
Dexhimer TS., Huang Shar-yin, Das BB and Pommier Y. Tyrosyl-DNA phosphodiesterase 1. 2011, Book: DNA Topoisomerases and Cancer: Publisher: Springer, NY USA .
 
Das BB, Ganguly A, Majumder HK. DNA topoisomerases of Leishmania: the potential targets for anti-leishmanial therapy. Book: Drug Targets in Kinetoplastid Parasites; Publisher: Springer, NY USA. 2008.

 



Teaching

NUCLEIC ACIDS: STRUCTURE & FUNCTION [3-0-0] 3

Overview; Structure and properties of RNA and DNA;DNA separation methods, chemical synthesis of DNA; the molecular basis of DNA replication, transcription and their regulation in prokaryotes and eukaryotes; Chromatin structure; DNA repair, excision repair, mismatch repair, post-replication repair, homologous recombination and non-homologous recombination; RNA structure and function; Ribozymes; experimental methods for studying DNA and RNA, recombinant DNA techniques, mutagenesis, protein-nucleic acids interaction.

Books/References: ï‚·

Lehninger Principles of Biochemistry (2012) Sixth edition, By Nelson & Cox, W.H. Freeman publisher. ï‚·

Nucleic Acids in Chemistry and Biology (2006) Third Edition, by G. Michael Blackburn, Royal Society of Chemistry Publishing. 

 

PhD course work for Biological Chemistry: 3 

Molecular Biology and Biological Chemistry.

 


Facilities


 

Laser Confocal Microscope with live cell facility

 

 

Inception of BBD Lab@IACS 2013

Inception of BBD Lab@IACS 2013


Open Positions

PhD positions are available in BBD laboratory

CSIR NET-JRF qualified candidates with good academic record and interested to peruse research in frontier areas of Molecular and Cell Biology are encouraged to apply for JRF position in the BBD laboratory.

Qualification of the applicants:

Candidates should have M.Sc. in Biochemistry, Genetics, Biology or Biotechnology or Chemistry. Experience in biochemistry or molecular biology lab is desirable. English written and oral communication skills are also required.

Please send your curriculum vitae, a letter describing your motivation to pursue this PhD project, and contact information for two referees as single pdf files to pcbbd@iacs.res.in. Applications will be considered until the position is filled. Questions regarding the project or position should be directed to the same email address.

 


Department


Project Students Alumni

(i) Ms. Preety Kaur,- St. Xaviers College,  Microbiology Department, Kolkata, 2015

(2) Mr. Souvik Mondal-  Biochemistry Department, Calcutta University, 2016

(3) Ms. Sumoyee Mukherjee-  St. Xaviers College,  Microbiology Department, Kolkata, 2016.

(4) Mr. Spandan Bhattachacharya- Department of Neuroscience, Calcutta University,

Kolkata 2016.

(5) Ms.Meghadipa GoswamiDepartment of Life Science, Christ University, Bangalore, 2017

(6) Ms. Samvidha Das, Dept. of Biotechnology, Techno India University, Salt Lake, West

Bengal. 2017.

(7). Ms.Kuheli Dasgupta, Dept. of Biotechnology, St. Xavier’s University, Kolkata, 2017

     (8). Ms. Sharbani Das, Dept. of Microbiology University of Calcutta, 2017

     (9). Ms. Priyadarshini Chatterjee, Molecular and Cellular Biochemistry, Brasenose 

                   College,University of Oxford, Radcliffe Square, Oxford OX1 4AJ, UK , 2018

    (10). Ms. Shreya Banerjee, Int-MSc-Phd Student intern for 1 year (2017-18)


Honors/Awards



Honors/Awards:

Honors/Awards

24. Elected Fellow of the National Academy of Science, India (NASI), 2020. 

23. ICMR (The Indian Council of Medical Research)- Dr Prem Nath Wahi Award 2019 for basic and/or clinical cytology or basic and/or preventive oncology research.

22. S. Ramachandran- National Bioscience Awards for Career Development award 2019-2020, Department of Biotechnology, Government of India.

21. Elected member of Guha Research Conference from the year 2019.

20. Elected Fellow of West Bengal Academy of Science & Technology (WAST), 2019.

19. Invited Speaker and travel award for International Ataxia-Telangiectasia Workshop 2019 (ATW2019), Houston Methodist Hospital, Houston,USA

18. Gordon Conference Travel Award and selected speaker 2018, DNA Topoisomerases in Biology and Medicine, Gordon Research Conference, South Hadley, MA, USA

17. Visiting fellow 2018 (July to September) at the National Cancer Institute, Center for Cancer Research, National Institutes of Health, USA.

16. “ISA-Senior Visiting Fellow-2016” at the Institute of Advanced Studies Alma Matter Studiorum, Department of Pharmacy and Biotechnology, University of Bologna, Italy, 2016.

15. UK-Wellcome Trust / DBT India alliance Intermediate fellow, 2013.

14. Ramanujan Fellowship 2013, Department of Science and Technology, Government of India.

13. Ramaligaswami Fellowship 2013, Department of Biotechnology, Government of India.

12. NCI outstanding Postdoctoral Fellow award (2012): Selected among top five fellows at National Cancer Institute, NIH, USA.

5. Gordon Conference Travel Award and selected speaker (2012), Salve Regina University, Newport, RI, USA.

11. Cold Spring Harbor meeting Travel award and selected speaker (2011), Cold Spring Harbor, NY, USA

10. Full Time Federal Employee (FTE) at National Institutes of Health, NCI, USA (2011).

9. HHMI mentor award (2010) for training HHMI sponsored summer interns.

8. Fellows Award for Research Excellence: Recognized for outstanding research at National Cancer Institute, NIH (2010-2011).

7. Fellows Award for Research Excellence: Recognized for outstanding research at National Cancer Institute, NIH (2009-2010).

6. NDDO Honorary Award Lecture 2010 in 8th International Symposium on Targeted Anticancer Therapies 2010, March 4-6. Washington DC, USA.

5. Postdoctoral fellowship award at National Cancer Institute, NIH (2006).

4. Best Poster award in International Training and Research in Emerging Infectious Diseases. Second Asian Regional Workshop 8-11 March 2005 at New Delhi, India.

3. Best Lecture award in Society of Biological Chemistry India at Digha. India (2004).

2. Senior Research fellowship award from Council of Scientific and Industrial Research (CSIR), India (2004).

1. Junior Research fellowship award for qualifying National Eligibility Test (NET/JRF) held by Council of Scientific and Industrial Research (CSIR), India (2001).

 


Contact Us



Contact:

Contact

Laboratory of Molecular Biology

School of Biological Sciences

Indian Association for the Cultivation of Science

2A & B, Raja S. C. Mullick Road, Jadavpur, Kolkata, India-700032

Phone: +91 33 2473 4971/3372 (Ext 2108)

Fax: +91 33 2473 2805

pcbbd@iacs.res.in

 







Alumni

Past Members:

1. Dr. Souvik Sengupta (DBT/RA), 2015

2. Dr. Papiya Majumder (CSIR/RA), 2016

3. Suparna M Basu (Project fellow), 2014. 

4. Dr. Subhendu K Das (PhD student), 2018

5. Dr. Ishita Rehman (PhD Student), 2019


Group News

BBD Lab 2022

BBD lab 2018

Lab lunch @ J W MARRIOT, Kolkata for joining of Jayashree and Ayesha

 


Research Activities


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