Cell cycle

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Cell Cycle

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Cell cycle

  1. 1. Cell CycleByAssociate Professor Dr Nilesh KumarMBBS, MS, MEd
  2. 2. 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
  3. 3. 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
  4. 4. 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
  5. 5. • 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
  6. 6. 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
  7. 7. 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
  8. 8. • 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
  9. 9. • 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
  10. 10. 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
  11. 11. • ―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
  12. 12. • 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
  13. 13. • 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)

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