ETD at Indian Institute of Science
Repository of Theses and Dissertations of Indian Institute of Science, Bangalore, India. The repository has been developed to capture, disseminate and preserve research theses of Indian Institute of Science.
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Insights Into Transcription-Repair Coupling Factor From Mycobacterium Tuberculosis - Swayam Prabha, *
Nucleotide excision repair (NER) is a highly conserved pathway involved in repair of a wide variety of structurally unrelated DNA lesions. One of the well characterized NER systems is from E. coli which involves UvrABC nucleases. NER consists of two related sub-pathways: global genomic repair (GGR), which removes lesions from the overall genome, and transcription coupled repair (TCR), which removes lesions from the transcribed strand of active genes. Bulky DNA lesions such as cyclobutane pyrimidine photodimers (CPD) induced by UV irradiation block RNA polymerase (RNAP) during transcription. In bacteria, a gene product of mfd called transcription repair coupling factor...
Studies On The Functional Roles Of Peptidase N, A M1 Family Member, During Stress And Infection - Bhosale, Manoj
The cytosolic protein degradation pathway, performed by ATP-dependent proteases and ATP-independent peptidases, plays important roles in several cellular activities, e.g. cell division, cell cycle progression, intracellular signaling, MHC class I antigen presentation, host-pathogen interactions, etc. The roles of ATP-dependent proteases during stress and infection have been studied in great detail but the functional roles of ATP-independent peptidases are not clearly understood. In this study, the functional roles of E. coli or S. typhimurium encoded Peptidase N (PepN), an ATP-independent enzyme belonging to theM1 family of metallopeptidases, were investigated. The thesis will address four different aspects.
(i) In the first part,...
The Mechanism Of Fragility Of The BCL2 And HOX11 Breakpoint Regions During t(14;18) And t(10;14) Chromosomal Translocations In Lymphoid Cancers - Nambiar, Mridula
Haematological cancers like leukemia and lymphoma are characterized by genetic abnormalities, specifically chromosomal translocations. Analyses of the translocation breakpoint regions in patients have shown that some loci in the genome are more susceptible to breakage than others. However, very little is known about the mechanism of generation of many such chromosomal translocations. In the present study, we have attempted to understand the mechanism of fragility of three regions, which are prone to breaks during translocations in follicular lymphoma (FL) and T-cell leukemia. The t(14;18) translocation in FL is one of the most common chromosomal translocations. Most breaks on chromosome 18...
Mechanism Of RAG Action As A Structure-Specific Nuclease : Implications In Genomic Instability In Lymphoid Cells - Naik, Abani Kanta
Recombination Activating Genes (RAGs) orchestrate the process called V (D) J recombination, which enables the vertebrate adaptive immune system to specifically recognize millions of antigens. During this recombination process, V (variable), D (diversity) and J (joining) gene segments of antibody (B cell receptor) and TCR (T cell receptor) join by different possible combinations to generate antigen receptor diversity. This unique site specific recombination process is actuated by lymphoid specific proteins called RAG1 and RAG2 (RAGs or RAG complex). RAGs recognize a conserved sequence motif flanking the above subexons called Recombination Signal Sequence (RSS). There are two types of RSS known...
Characterization Of HP1369-HP1370 From Helicobacter Pylori : A Novel ε Type N6 –Adenine Methyltransferase - Chaudhary, Awanish Kumar
Helicobacter pylori is one of the most genetically diverse bacterial species that successfully colonizes at least 50% of the world population. It has been associated with humans for thousands of years and most probably evolved from ancestral gastric Helicobacter species in early mammals. One of the important characteristics of this pathogen is the degree of allelic diversity and genetic variability which helps it to adapt and colonize. Phase variation is one of the mechanisms used by H. pylori to generate variation. The presence of homopolymeric nucleotide or dinucleotide repeats in an ORF make it prone to frequent length changes as...
Exploring The Role Of Purinergic Signaling In T Cell Activation - Bhate, Monali M
Adenosine 5’ triphosphate (ATP) is a molecule central to life for its role as the
cellular energy currency, and a purine nucleotide which serves as a building block of RNA. Thus, on the backdrop of an indispensible intracellular role of ATP, its identification as an extracellular signaling molecule in early 1970s came as a surprise. A novel doctrine, termed as ‘purinergic signaling’, was thus put forth. By definition, purinergic signaling consists of
the signaling events triggered by binding of extracellular ATP- a purine nucleotide, and its breakdown products (viz., ADP, AMP, and adenosine) to their cognate receptors, which in turn are termed...
Production Of Anticancer Drug Taxol And Its Precursor Baccatin III By Fusarium Solani And Their Apoptotic Activity On Human Cancer Cell Lines - Chakravarthi, B V S K
Taxol (generic name paclitaxel), a plant‐derived antineoplastic agent, was
originally isolated from the bark of the Pacific yew, Taxus brevifolia. Obtaining
taxol from this source requires destruction of trees. It has been used alone or in
combination with other chemotherapeutic agents for the treatment of breast,
ovarian as well as many other types of cancer, including non‐small cell lung
carcinoma, prostate, head and neck cancer, and lymphoma, as well as AIDSrelated
Kaposi’s sarcoma. The mode of action of taxol against a number of human cancer cells is by preventing the depolymerization of tubulin during cell division. This molecule increases microtubule stability in the cell and induces...
Processing Of DNA Recombination And Replication Intermediates By Mycobacterium Tuberculosis RuvA And RuvB Proteins - Khanduja, Jasbeer Singh
Homologous recombination (HR) is a highly conserved cellular process involved in the
maintenance of chromosomal integrity and generation of genetic diversity. Biochemical and genetic studies have suggested that HR is crucial for repair of damaged DNA arising from various endogenous or exogenous assaults on the genome of any organism. Further, HR is vital to repair fatal DNA damage during DNA replication. An instructive example of cross-talk between the processes of DNA recombination and replication can be construed in the processing of replication/recombination/repair intermediates. The impediment(s) to the progression of DNA replication fork is one of the underlying causes for increased genome...
Insights Into The Mechanism Of Polyprotein Processing Of Sesbania Mosaic Virus And Characterization Of The Polyprotein Domains - Nair, Smita
1. Viruses are obligate parasites that hijack the host cell machinery to synthesize
their own gene products and for their propagation. In order to establish a
successful viral infection, viruses have evolved different strategies to evade
host check points. Further more, their success also relies in employing varied
strategies to express maximum number of functional proteins from their small
constrained genome. Polyprotein processing is a widely used strategy of
expression by many plant viruses. With limited information available on this
aspect for sobemoviruses, the present study was undertaken.
2. The present thesis deals with the mechanism of Sesbania mosaic virus (SeMV) polyprotein processing and functional characterization of the...
Molecular Cloning And Characterization Of A Calcium-Depdendent Protein Kinase Isoform ScCPK1 From Swainsona Canescens - Srideshikan, S M
Plants are constantly exposed to pathogens and various environmental stresses, such as cold, salinity and drought. Plants normally respond rapidly to these biotic and abiotic stresses. Efficient perception of biotic and abiotic stresses and cell programmed signaling mechanisms for appropriate responses are important for growth and survival of plants. Calcium is an important second messenger in signaling pathways that respond to environmental stresses, pathogen attack as well as hormonal stimuli (For review, see DeFalco et al., 2010; Reddy and Reddy, 2004; Sanders et al., 2002). The transient increase of cytosolic free calcium concentration has been shown in a variety of...
Biochemical Characterization Of Heat Shock Protein 90 From Plasmodium Falciparum - Pallavi, Rani
Molecular chaperones are a group of proteins which maintain cellular homeostasis by assisting de novo protein folding and their refolding to native state after destabilization due to external stress. They are also known as heat shock proteins as they were first discovered as a response to heat stress. It is now well established that the function of this group of proteins is not only restricted to protein homeostasis but also extends to diverse cellular processes such signal transduction, development and differentiation.
Heat shock protein 90 (Hsp90) is one of the most abundant molecular chaperones that is highly conserved from prokaryotes...
Helicobacter Pylori Restriction-Modification Systems : Possible Roles Beyond Genome Protection - Kumar, Ritesh
Helicobacter pylori is one of the most potential and successful human pathogen which colonizes atleast 50% of world population. One of the important characteristics of this pathogen is the degree of allelic diversity and genetic variability which helps it to adapt and colonize. Phase variation is one of the mechanisms used by Helicobacter pylori to generate variation, where presence of homopolymeric nucleotide or dinucleotide repeats in an ORF make it prone to frequent length changes as a consequence of slipped strand mispairing mediated mutagenesis.
An important feature of H. pylori biology is the presence of a large number of Restriction-Modification (R-M)...
Understanding Heat Shock Protein 90 Biology And Exploring Its Potential As A Target Against Neglected Protozoan Diseases - Roy, Nainita
Cells invest a lot of energy in order to get their proteins to fold correctly and attain functionality. It is the functional proteome of a cell that defines the ‘life of a cell’. Cells have therefore employed dedicated machinery called chaperones to enable protein folding. One class of these chaperones is heat shock proteins named so because they were initially discovered to be heat inducible and particularly important during heat stress. However the role of heat shock proteins has now been extended from merely being important for stress tolerance. Heat shock proteins are prominently involved in maintaining the correct folding...
Functional Characterization And Regulation Of UvrD Helicases From Haemophilus Influenzae And Helicobacter Pylori, And Recj Exonuclease Fron Haemophilus Influenzae - Sharma, Ruchika
DNA repair processes are crucial for mutation avoidance and the maintenance of genetic integrity in all organisms. Organisms rely on repair processes to combat genotoxic stress imposed by hostile host environment, and sometimes by therapeutic agents. Most pathogens rapidly generate genetic variability to acquire increased virulence and evade host immune response. Therefore, there needs to exist a fine balance between mutation avoidance and fixation, which is perhaps regulated by repair processes. Haemophilus influenzae and Helicobacter pylori contribute significantly to morbidity and mortality caused by bacteria worldwide. H. influenzae is an obligate commensal of upper respiratory tract with the potential to...