molecular mechanisms in cell division

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molecular mechanisms in cell division

  1. 1. Dr Sufyan Akram
  2. 2. Overview of Cell DivisionPhases of Cell DivisionMolecular mechanisms in Cell DivisionImportant structures and key components in DNAsynthesisDNA polymerases and the process of DNA replicationProof reading and repairRegulation of Cell Cycle
  3. 3. Most eukaryotic cells willpass through an orderedseries of events in which thecell duplicates its contentsand then divides into twocellsThis process of cell divisionin multicellular organismsmust be highly ordered andtightly regulated
  4. 4. Mitosis is the process by which a eukaryotic cellduplicates its DNA and then divides into twodaughter cells, each of which contains the exactgenetic material as the mother cell and getsroughly an equal share of other cellularcomponentsIf the DNA of a human cell were uncoiled andstretched, it would extend approximately 2meters!
  5. 5. Meio: to reduceA form of nuclear division in which thechromosome number is halved from the diploidnumber (2n) to haploid number (n)It is preceded by DNA replication duringinterphase in the parent cell. This is followed by2 cycles of nuclear division and cell divisions-Meiosis I and Meiosis II
  6. 6. Mitosis generates twogenetically identical diploiddaughter cellsMeiosis generates four haploiddaughter cells, none of which aregenetically identical
  7. 7. Starting from a single-celled zygote… An adulthuman being has approximately 100,000 billioncellsCell division does not stop with formation ofmature organism, but continues throughout itslifeTens of millions of cells undergo division at anygiven moment in an adult human. This amount ofdivision is needed to replace cells that have agedor died
  8. 8. Two major cell cycle phases - based on cellactivities readily visible under light microscope:Interphase - occupies bulk of cycle; divided into G1(first gap), S (synthesis) & G2 (second gap)M phase – M for "mitotic"; this stage includes mitosis(duplicated chromosomes are separated into 2 nuclei)& cytokinesis (entire cell & its cytoplasm divide into 2daughter cells)
  9. 9. G1 - growth phase 1S - DNA synthesisG2 - further growthM - cell divisionMitosis:– prophase, prometaphase,metaphase, anaphaseand telophaseCytokinesisInterphaseMitoticphase
  10. 10. G1 (G=gap) is the interval between thecompletion of mitosis and the beginning of DNAsynthesisDuring G1, the cell monitors its ownenvironment and size before it commits itself toDNA replication. Cells in G1 (if not committed toDNA replication) can pause their progress andenter a specialized resting state G0S phase - replication of nuclear DNAInterphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana Telo
  11. 11. G2 is the second “Gap” phase:Nucleus well defined and bound by nuclearenvelopeOutside nucleus are two pairs of centriolesformed during early interphaseMicrotubules extend from centrioles in a radialarray called astersInterphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana Telo
  12. 12. Interphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana TeloProphaseChanges occurs in both nucleus and cytoplasmNucleus: Chromatin fibres become more tightlycoiled and condense into discrete chromosomes.The duplicated chromosome appears as 2identical sister chromatids joined by centromereCytoplasm: formation of mitotic spindle begins
  13. 13. Interphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana TeloPrometaphaseNuclear envelope develop fragments.Microtubules can now invade the nucleus andinteract with the chromosomesMicrotubule attach to kinetochore on eachchromosomes centromereAsters, radiate from centrioles and anchorthemselves to membrane plasma
  14. 14. Interphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana Telo
  15. 15. Interphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana TeloMetaphaseCentrioles at opposite poles of the cellChromosome convene on the metaphase plate(imaginary plane of equal distant betweenspindles of two poles)
  16. 16. Interphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana Telo
  17. 17. Interphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana TeloAnaphaseBegins when paired centromeres of eachchromosome separate, liberating each sisterchromosome from one another (each chromatidis considered one full fledged chromosome)Chromosomes begin moving along microtubuletoward opposite poles of the cell
  18. 18. Interphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana TeloTelophaseNucleolus begins to form at the two poles of thecells. Nuclear envelopes are formedChromatin fibre of each chromosome becomeless tightly coiledMitosis ends and cytokinesis begins
  19. 19. Interphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana TeloCytokinesisOccurs by a process called cleavage: begins witha cleavage furrow, a shallow grove near themetaphase plateIn cytoplasmic side of the furrow, are contractileactin proteins. As the actin microfilamentcontract, its diameter shrinks, cleavage furrowdeepens until cell pinched into two
  20. 20. Interphase Mitotic phaseG1 S G2 Pro Prometa Meta Ana Telo
  21. 21. DNA replication begins at specific locations inthe genome, called "origins“Unwinding of DNA at the origin, and synthesis ofnew strands, forms a replication fork. In additionto DNA polymerase, the enzyme that synthesizesthe new DNA by adding nucleotides matched tothe template strand, a number of other proteinsare associated with the fork and assist in theinitiation and continuation of DNA synthesis
  22. 22. The replication fork is a structure that formswithin the nucleus during DNA replication. It iscreated by helicases, which break the hydrogenbonds holding the two DNA strands togetherThe resulting structure has two branching"prongs", each one made up of a single strand ofDNA
  23. 23. DNA polymerases are a family of enzymes thatcarry out all forms of DNA replicationTo begin synthesis, a short fragment of DNA orRNA, called a primer, must be created and pairedwith the template DNA strandDNA polymerase then synthesizes a new strandof DNA by extending the 3 end of an existingnucleotide chain, adding new nucleotidesmatched to the template strand one at a time viathe creation of phosphodiester bonds
  24. 24. The PCR does in the test tube what everybacterium does in its tube of media or on anagar-plate and each of us do every day: we allproduce billions of exact copies of our own DNA;AMPLIFYING our DNA millions of timeThe enzyme DNA polymerase was discovered inthe 1950s and our knowledge of the process hasbeen increasing ever since
  25. 25.  TARGET DNA to be copied. In theory only a singlemolecule is needed A set of short (15 to 40 bases) single stranded PRIMERSof DNA, that will bind to complementary regions of theopposing stands of the target DNA molecule An excess of the 4 nucleotide triphosphates, ATP, GTP,CTP, TTP The enzyme, DNA polymerase Various buffers and cofactors like magnesium ionsrequired by DNA polymerase
  26. 26. Double helix target DNA strands are separated sothe primers could bind and the DNA polymerasecould functionHeat separates DNA strands and thatcomplementary strands then rejoin through basepairing when the temperature is subsequentlylowered
  27. 27.  Lowering the temperature enough to allow theprimers, which were small and in vast excess, tobind (ANNEAL) to their respectivecomplementary target DNA sequence DNA polymerase allows polymerization reactionwith the triphosphate nucleotides to occur
  28. 28. 5′3′3′5′5′3′3′5′5′3′3′5′5′5′3′3′123DNA
  29. 29. 5′3′3′5′5′5′3′3′5′3′3′5′5′5′3′3′45
  30. 30.  The DNA polymerase fills in the missing portionof each strand making two new double strandedregions of DNA The whole process is repeated several times thusyielding exponential amount of DNA strands2 4 8 16 32 After 12 cycles… 8192After 20 cycles… 2097152
  31. 31. Beginning with a single piece of DNA, PCR can generate100 billion identical copies of a specific DNA sequence !!!
  32. 32. PCR takes place in a tube which is kept in amachine called “thermal cycler”
  33. 33. For all living eukaryotic organisms it is essentialthat the different phases of the cell cycle areprecisely coordinatedErrors in this coordination may lead tochromosomal alterations. Chromosomes or partsof chromosomes may be lost, rearranged ordistributed unequally between the two daughtercells
  34. 34. NutrientsGrowth factorsCell size Regulatory proteins& Protein kinasesCell-cell contact
  35. 35. Much of the control of the progression through thephases of a cell cycle are exerted at checkpointsThere are many such checkpoints but the threemost critical are those that occur near the end ofG1 prior to S-phase entry, near the end of G2 priorto mitosis, and at metaphase…
  36. 36. G0G2 CheckpointG1 CheckpointMetaphaseCheckpointIs cell big enough?Is environment favourable?Is all DNA replicated?Is cell big enough?Is environment favourable?Are all chromosomesaligned on spindle?

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