Biennial Report 2005-2007 - Saha Institute of Nuclear Physics

Biophysical Sciences 1996.1.1.3 Regulation of micro RNA and its role in neurodegenerative diseaseMicroRNAs are small 17-22 nucleotide RNAs, which negatively regulate the gene expression bybinding to 3’-UTR of mRNAs, either by degrading the mRNA or interfering with translation ofthe genes. To identify the role of micro RNA in deregulation of the genes observed in Huntington’sdisease and the role of HIPPI, a molecular partner of huntingtin interacting protein Hip-1, inregulation of micro RNAs, we have been studying the expressions of 157 micro RNAs in cellsexpressing huntingtin (htt) exon1 with 80 glutamines and cell line expressing HIPPI. Preliminaryresults revealed that several microRNAs are up-regulated in cells expressing HIPPI and interestinglymany of them contain HIPPI binding motif to their upstream. In continuation to our previouswork whereby we have studied the Single Nucleotide Polymorphism (SNP) associated with ChronicMyeloid Leukemia (CML), we are studying whether genetic polymorphisms in micro RNAs playany role in the regulation their expressions in CML.Mithun Sinha, Nitai P BhattacharyyaSG6.1.1.4 Role of PARP-1 in apoptosis and telomerase regulationTo identify the function of PARP-1, we have earlier shown that inhibition of PARP-1, either byknocking down the expression of the gene by siRNA or inhibitor like benzamide, decreased thetelomerase activity and increased apoptosis. Decreased telomerase activity and increased apoptosiscould be mediated by poly (ADP-ribosyl)ation of TERT and caspase-8. We now have confirmedthese results using several specific inhibitors like minocycline. Minocycline has further been shownto inhibit PARP-1 activity. We have also shown that curcumin treatment inhibits telomeraseactivity and increased apoptosis induction in leukemic cells. Decreased telomerase activity is likelyto be due to inability of TERT to translocate into the nucleus. DNA binding domain and thecatalytic domain of PARP-1 has been cloned separately. These are now being used to identify theroles of these domains in the regulation of apoptosis. (This project was partially supported byDST, Govt of India).Madhumita Roy†, Nitai P Bhat-C&MBUtpal Ghosh, Rona Banerjee, Sutapa Chakraborty†,tacharyya6.1.1.5 Molecular Diagnosis and genetics of neurological diseases caused by the expansionof triplet repeatsWe have been continuing detection of CAG/CTG repeat expansions that cause neurodegenerativedisease like various spinocerebellar ataxias (SCA) and Huntington’s disease (HD) in clinically diagnosedpatients sent to us by neurologists from different parts of the country. During this period, wehave identified altogether 22 expansion of CAG repeats at SCA1, SCA2 and SCA3 loci and 11 CAGRepeat expansions at HD locus among patients. To identify the origin of mutation in HD patient,we used polymorphic markers namely D4S127 (di-nucleotide CA repeat), rs1313770 (SNP), rs82334(SNP), insertion (+)/deletion (-) of codon 2642 (GAG) and polymorphic CCG repeat variation inthe immediate vicinity of the CAG repeat tract among 62 unrelated HD patients and 55 normalindividuals originated from the same geographical and ethnic origin. Using these five loci, haplotypeswere constructed by the software GENECOUNTING. The CAG repeat numbers among the