Molecular Mechanism Governing the CRISPR Adaptation in CRISPR-Cas Type I-E System

dc.contributor.authorYoganand, K N R
dc.date.accessioned2023-01-12T07:35:10Z
dc.date.accessioned2023-10-19T11:05:46Z
dc.date.available2023-01-12T07:35:10Z
dc.date.available2023-10-19T11:05:46Z
dc.date.issued2021
dc.descriptionSupervisors: Anand, B and Swaminathan, Rajaramen_US
dc.description.abstractCRISPR-Cas based adaptive immunity protects the genome of bacteria and archaea from the attack of foreign genetic elements such as bacteriophages and plasmids. A specialized region on the genome termed CRISPR locus is the activity center for this small RNA-based immune response. CRISPR locus comprises numerous short repeats interspaced by equal-sized spacers and an AT-rich leader. When the bacteriophage attacks the bacterium, the bacteriophage DNA is broken down into small fragments (prespacers), which are then integrated into the CRISPR array as spacers. These bacteriophage derived spacers act as DNA-based infection memory – akin to protein-based antibodies in higher organisms like humans – to counter recurrent infection. The process of generating infection memory is called CRISPR adaptation. The spacers derived from the invader are precisely sized and always integrated at the leader-proximal repeat in the CRISPR array. In this work, the molecular mechanism of CRISPR adaptation in type I-E CRISPR-Cas system is addressed using model bacterium Escherichia coli. In the type I-E CRISPR-Cas system, two universally conserved proteins Cas1 and Cas2, form an integrase complex and catalyze the CRISPR adaptation. Exonucleases trim the Cas1-2 bound DNA to produce a 33 bp prespacer that holds the infection memory. A nucleoid protein called IHF cooperates with the Cas1-2-prespacer integrase complex to store the infection memory. IHF interacts with the CRISPR leader and restructures this region to generate a cognate binding site for Cas1-2-prespacer at the leader proximal repeat. This process allows the integration of 33 bp DNA fragment in a sequential order into the CRISPR array. These intricate mechanistic details of infection memory generation demystify how bacteria use the CRISPR-Cas system to recognize and counter the recurrent invasion of bacteriophages.en_US
dc.identifier.otherROLL NO.11610606
dc.identifier.urihttps://gyan.iitg.ac.in/handle/123456789/2242
dc.language.isoenen_US
dc.relation.ispartofseriesTH-2779;
dc.subjectProkaryotic Adaptive Immunityen_US
dc.subjectCRISPR-Casen_US
dc.subjectCRISPR Adaptationen_US
dc.subjectCas1-Cas2en_US
dc.subjectPrespacer Processingen_US
dc.subjectPolarized Prespacer Integrationen_US
dc.subjectIHFen_US
dc.titleMolecular Mechanism Governing the CRISPR Adaptation in CRISPR-Cas Type I-E Systemen_US
dc.typeThesisen_US
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