Scientist D

Description of Research:

Our laboratory studies the role played by ubiquitin-proteasome system in regulation of physiological pathways like cell cycle, DNA damage response, apoptosis and autophagy. Ubiquitin-proteasome system is a major post-transcriptional regulatory mechanism for protein homeostasis in the cell. The ubiquitin modification carried out by enzymes called E3 ubiquitin ligases mark the regulatory proteins for proteasomal degradation or functional activation/inactivation. Cells have also evolved another class of enzymes called Deubiquitinases (DUBs) to antagonize the ubiquitination of proteins by E3 ligases. E3 ligases and DUBs thus regulate the protein turn over and control the functioning of physiological pathways. The laboratory is using genetic and proteomic approaches in exploring the mechanism underlying the protein homeostasis by E3 ligases and DUBS in Cell cycle, DNA damage,  apoptosis, autophagy and Cancer. 

Peer-reviewed Publications:

1.   Dar MA, Sharma A, Mondal N, Dhar SK. Molecular cloning of apicoplast-targeted Plasmodium falciparum DNA gyrase genes: unique intrinsic ATPase activity and ATP-independent dimerization of PfGyrB subunit. Eukaryotic Cell, 2007,6,398-412.   PMID: 17220464

 2. Nitharwal RG, Paul S, Dar A, Choudhury NR, Soni RK, Prusty D, Sinha S, Kashav T, Mukhopadhyay G, Chaudhuri TK, Gourinath S, Dhar SK. The domain structure of Helicobacter pylori DnaB helicase: the N-terminal domain can be dispensable for helicase activity whereas the extreme C-terminal region is essential for its function. Nucleic Acids Research, 2007, 35, 2861-74.    PMID: 17430964

3. Sharma A, Nitharwal RG, Singh B, Dar A, Dasgupta S, Dhar SK. Helicobacter pylori single-stranded DNA binding protein--functional characterization and modulation of H. pylori DnaB helicase activity. FEBS J, 2009, 276, 519-31. PMID19087193

4. Gupta A, Mehra P, Deshmukh A, Dar A, Mitra P, Roy N, Dhar SK. Functional dissection of the catalytic carboxyl-terminal domain of origin recognition complex subunit 1 (PfORC1) of the human malaria parasite Plasmodium falciparum. Eukaryotic Cell, 2009, 8, 1341-51.  PMID: 17430964

5.   Dar A, Prusty D, Mondal N, Dhar SK. A unique 45-amino-acid region in the toprim domain of Plasmodium falciparum gyrase B is essential for its activity. Eukaryotic Cell, 2009, 8, 1759-69. PMID: 19700639

 6.   Dar A^#, Prusty D^#, Priya R, Sharma A, Dana S, Choudhury NR, Rao NS, Dhar SK. Single-stranded DNA binding protein from human malarial parasite Plasmodium falciparum is encoded in the nucleus and targeted to the apicoplast. Nucleic Acids Research, 2010, 38, 7037-53.  PMID: 20571080         # Co-first Authors

7.  Winkler DD, Zhou H, Dar MA, Zhang Z, Luger K. Yeast CAF-1 assembles histone (H3-H4)2 tetramers prior to DNA deposition. Nucleic Acids Research, 2012, 40, 10139-49. PMID:  2294163

8.  Jha S, Gupta A, Dar A, Dutta A. RVBs are required for assembling a functional TIP60 complex. Molecular and Cellular Biology, 2013, 33, 1164-74. PMID: 23297341

9. Snow CJ, Dar A, Dutta A, Kehlenbach RH, Paschal BM. Defective nuclear import of Tpr in Progeria reflects the Ran sensitivity of large cargo transport. The Journal of Cell Biology, 2013, 13, 541-57. PMID:  23649804

10. Dar A, Shibata E, Dutta A. Deubiquitination of Tip60 by USP7 determines the activity of the p53-dependent apoptotic pathway. Molecular and Cellular Biology, 2013, 33, 3309-20. PMID: 23775119

11. Dar A^#, Shibata E^#, Dutta A. CRL4Cdt2 E3 Ubiquitin Ligase and PCNA Cooperate to Degrade Thymine DNA Glycosylase in S-phase. Journal of Biological Chemistry, 2014, 33, 23054-64. PMID:24962565.                            # Co-first Authors

12. Dana S, Prusty D, Dhayal D, Gupta MK, Dar A, Sen S, Mukhopadhyay P, Adak T, Dhar SK. The potent Anti-malarial activity of Acriflavine in vitro and in vivo. ACS Chemical Biology, 2014,9, 2366-73.        PMID: 25089658

13. Dar A, Wu D, Lee N, Shibita E, Dutta A. 14-3-3 proteins play a role in the cell cycle by shielding Cdt2 from ubiquitin-mediated degradation. Molecular and Cellular Biology, 2014, 34, 4049-61.  PMID: 25154416

14.  Dar A#, Kiran S#, Singh S# , Lee KY, Dutta A. The Deubiquitinase USP46 is essential for proliferation and tumor growth of HPV transformed cancers. Molecular Cell, 2018, 72 (5), 823-835                                              #Co-first Authors

15. Prusty D, Gupta N, Upadhyay A, Dar A, Naik B, Kumar N, Prajapati VK.  Asymptomatic malaria infection prevailing risks for human health and malaria elimination. Infect Genet Evol.2021 Jun 30;93:104987

Patents:

 1. Suman Kumar Dhar, Srikanta Dana, Ashraf Dar, Dhaneswar Prusty, Pritam Mukhopadyay.  Method of screening anti-plasmodial activity of acriflavin and acriflavin as an anti-malarial agent. 2016.  (US 9,375,426 B2)

Interdisciplinary Book Chapters: 

1. Bashir M and Dar A* . Mulberry: From root to fruit with antidiabetic properties (2021). Antidiabetic plants for drug discovery. Taylor & Francis, USA

2. Maqbool R, Shah H, Ashraf T, Bashir M and Dar A*. Transposable elements and DNA repair at the cellular level (2021). Plant Transposable Elements. Taylor & Francis, USA

3. Shah H, Manzoor A and Dar A*. Computational tools and approaches for CRISPR/Cas technology (2021). Crispr/cas-mediated genome editing in Plants. Taylor & Francis, USA

4. Ashraf T, Shah H, Maqbool R, Manzoor A and Dar A*. Mechanism of RNA Splicing. Alternative Splicing and Cancer (2022). Taylor & Francis, USA

5. Shah H, Manzoor A, Ashraf T, Maqbool R and Dar A*. MicroRNAs in Plants and Animals: Converging and Diverging Insights. (2022). Taylor & Francis, USA

6. IA Dar, M Bashir and A Dar*. Plant microRNAs: physiological significance in plants and animals (2022). Taylor & Francis, USA

7. A Manzoor, T Ashraf, H Shah, R Maqbool, R Kaul, A Dar*. MicroRNAs and other non-coding RNAs in plant epigenetics. (2022). Taylor & Francis, USA