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Cell cycle
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Cell Cycle

Cell Cycle

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    Cell cycle Cell cycle Presentation Transcript

    • Cell CycleByAssociate Professor Dr Nilesh KumarMBBS, MS, MEd
    • Objectives• At the end of the lecture the studentswould be able to explain—• What is cell cycle?• Phases of cell cycle• Check-points at each phase• Regulation of cell cycle• Relationship of cell cycle & cancer
    • Introduction• Definition• Reproduction & division of cell is feature of all livingthings.Cell cycle or cell-division cycle, is the series of events thattake place in a cell as a controlled set of events, whichleads to cell growth and division• Prokaryotic Cell (Bacteria—without nucleus) cell cycleoccurs as ‗Binary Fission‘• Eukaryotic cell (with nucleus, human, animal & plantcells) cell cycle has 2 PRINCIPAL PERIODSINTERPHASEMITOTIC PHASE
    • Cell division is an unique & essential process by whichfertilized egg forms mature organismAlso hair, skin, blood, intestinal cells get renewed―Before dividing into 2 new cells the cell must copy its genetic informationso that the new cell can get everything they need‖—Cytoplasmicorganelles, membranes, structural proteins, RNA all are replicatedcontinuously in cell cycledoubling of cell size
    • • 4 distinct phases• G1 Phase (starting phase or Growthphase)Gap between Mitosis of precedinground of cell cycle & DNAsynthesis of current cycle –cells increase inSize, Growth phase for RNA—eachChromosome with SINGLE molecule DNA• S PhaseDNA synthesis & replication,amount of DNA doubled –eachChromosome—2 sister chromatids• G2 PhaseGap between the DNA synthesis &decision to divide—check point controlbefore mitosis (Spindle in formed• M phaseCell division (Mitosis) & formation 2Diploid cells (Cytokinesis)G1+S+G2 Phases = INTERPHASE(12 to 24 Hours in a mammaliancell)M Phase 1 to 2 hoursPhases of cell cycle
    • G0 Phase• G0 Phase-- Post-mitotic quiescent andsenescent stage[non-proliferative cells like NEURON mayremain in this stage for a long time]• If DNA damage (Cancer)  cellularsenescence cell degradation• Semi-permanent G0 phase—kidney orliver disease
    • Check-Points• G1 Phase―Not Responsive to Mitogenic Stimuli‖Biosynthesis process--- use of 20 amino acids to form millions ofproteins (to be utilised during S-phase)Controlled by p53 gene---‖any resultant damage from previous cellcycle has been repaired‖―restrict entry of cells with damaged DNA into S phase‖• S Phasesynthesis is completed quickly so that the base pairs sensitive toexternal factors such as drugs mutagens (nicotine) are not affected• G2 PhaseG2 checkpoint control mechanism ensures---everything is ready to enterthe M (mitosis) phase and divides, all damage to DNA done in previouscycle repaired• Two cell-cycle checkpoints control the order and timing of cell-cycle transitionsG1 S and G2M
    • • Chromosomes are in single copies, DUPLICATED onlyonce per cycle, in S phase• Duplication & division should be carried out withprecision• Important because ‗Genetic information contained inDNA‘ & ‗Near-perfect transmission is important forevolution of species‘• Hence a ‗cell-cycle control system‘ regulates timing &coordination
    • • Paul Nurse won Nobel Prize in 2001• Discovery of Cyclin & & CDK• Cyclin & CDK--Protein kinases cause ‗Phosphorylation‘ ofspecific proteins in the cell required for transition to nextstage• Thus stimulate cell cycle progression (negativelycontrolled; CDK inhibitors—suppress cell cycle in DNAdamage)• 4 types Cyclin : A, B, D, E• Example:MPF (maturation promoting factor) is Cyclin-CDK complexChromosomal Condensation by phosphorylation of Histoneinitiates G2—M phaseRegulation of Cell Cycle
    • Cyclin Kinases FunctionD CDK4,CDK6Restriction point at G1—S phaseE, A CDK 2 DNA synthesis , early S phaseB CDK 1 Transition at G2—M phase• G1 phase is a criticalstage• Lot of extracellularcues• Either go for celldivision or go to G0• Control of DNAintegrity before theonset of DNAreplication
    • • ―MITOGENS‖• Growth Factors, Hormones, Cell to Cellinteractions• Binds to specific receptors on cellsurface Phosphorylation of targetproteinsCascade Phenomenon causeschanges in gene expressionExtracellular Regulation of Cell Cycle
    • • Chemical exposure—Benzene, Nitrosamines• Radiation (UV)• Viral DNA exposure• Inherited defects• ‗DNA Mutations‘– Expression of genes or Expression of genesCell cycle control affected  Genomic DNA alteredphenotype of cell changed from normal to malignantCell Cycle & Malignancy
    • • Oncogenes: mutated normal cellular genesproducing tumours• Tumour Suppressor genes: genes in normalcells, lost activity growth of tumour• Apoptotic Regulator genes: genes in normal cellscontrolling apoptosis (natural cell death)• DNA repair genes: maintain genomic integrity; ifrepair not possible, DNA damage passed on tosubsequent cell generationsRelated Genes in Cancer (affecting cell cycle)