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cell cycle and control checkpoints throght cyclin cdk complex
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- 2. What is thecell cycle? All cells are derived from pre-existing cells Cell cycle: defined as ordered sequences of events that occurs in the cell in preparation of cell division. The Cell cycle has two basic Function : Copying cellular components and DNA duplication Dividing the cell so that components are distributed evenly to the daughter cells The alternating “growth” and “division” activities of the cell is called the “cell cycle”. Cell division is an integral part of the cell cycle.
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- 4. •In unicellular organisms,division of one cell reproduces the entire organism (reproduction) •Multicellular organisms depend on cell division for • Growth (increase in numbers) and maintained and repaired (adults renewal e.g. liver, skin). Why the cell division occur? Are all cells divide? •NO some cell can’t divide e.g eye lens, nerve cell, heart cells. Theses cells maintained and repaired by replacing the intracellular component.
- 5. Types of CellReproduction 5 Asexual reproduction involves a (smatic cell) single cell dividing to make 2 new, identical daughter cells (eg.Mitosis) Sexual reproduction involves two cells (egg & sperm) joining to make a new cell (zygote) that is NOT identical to the original cells ( e.g.Meiosis ) All diploid chromosomes is homologous except six chromosome in male (y from father & x from mother) Diploid (46 chr) Haploid (23 chr)
- 6. The “growth”activity corresponds to “Interphase”. cell growth and copying of chromosomes in preparation for cell division The division activity corresponds to “M phase”. What is the cell cycle basic function? (mitosis andcytokinesis) Interphase M Interphase M Interphase G1 S G2 M G1 S G2 M G1 S G2
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- 8. Interphase (about90% of the cell cycle) is span between cell division can be divided into subphases G1 phase (“first gap”) the cell size increased S phase (“synthesis”) chromosomes are duplicated (longest phase) G2 phase (“second gap”) cell prepared to divide © 2011 Pearson Education, Inc. Interphase
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- 10. Interphase G1 & G2gap: -The cell grows and mass protein and organelles are duplicated. -The cell monitor the internal and external environment to ensure the condition suitable and prepare for S and M. -In unfavorable extracellular condition the cell delay progression through G1. -The cell may enter in G0 (resting state) it may stay in until die or until the condition become favorable and cell can row and divide.
- 11. Interphase In yeast“Start” is at the end of G1; at this point the cell is committed to DNA synthesis. In mammals, this is called the “restriction point”. This point late in G1 is a “checkpoint”; a cell will exit the cell cycle if certain requirements to proceed to synthesis are not met. After passing this point even the signal stimulating cell growth removed the DNA will synthesis. A second restriction point occurs in G2 before entry into mitosis.
- 12. Interphase: G1 Eventsduring G1 1 st stage of Cell growth after cell division Preparation of chromosomes for replication Duplication of cellular components (cytoplasm and organel) Cell carries on its normal metabolic activities G1 checkpoint (or restriction point); cell commits to division or exits from cell cycle
- 13. S- phase Theinstructions for making cell parts are encoded in the DNA, so each new cell must get a complete set of the DNA molecules DNA must be copied or replicated before cell division Each new cell will then have an identical copy of the DNA 13 Original DNA strand Two new, identical DNA strands
- 14. Duplicated chromosomes arecalled chromatids & are held together by the centromere 14 Called Sister Chromatids S- phase
- 15. DNA replication Duplication of the centrosome The centrosome is located near the nucleus of the cell and contains the microtubule organizing center MTOC in animal cells. It contains two centrioles surrounding by loose collection of protein that migrate to the poles before cell division and serve to organize the spindle. S- phase
- 16. Interphase: G2 2nd Cell growth stage Occurs after DNA has been copied All cell structures needed for division are made (e.g. centrioles) Both organelles & proteins are synthesized Checkpoint (restriction point) for entry into M phase
- 17. Mitosis 17 Daughter Cells DNA Copied Cells Mature Cells preparefor Division Cell Divides into Identical cells
- 18. Mitosis (celldivision) is highly regulated process include (karyokinesis) nucleus division and cytoplasm division cytokinesis. Only occurs in eukaryotes Doesn’t occur in some cells such as brain cells Mitosis stage conventionally divided into five phases Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis overlaps the latter stages of mitosis © 2011 Pearson Education, Inc. Mitosis phase
- 19. PROPHASE the firstphase in mitosis and longest phase of mitosis. THREE THINGS TO LOOK FOR: 1.chromosomes can be visible under light microscope as two chromatids, in the shape of an “X” (chromatin condenses to form chromosomes) 2.Nuclear envelope dissolves ( begin disagrregate) 3.Centrioles are present with some spindle fibers and the sister chromatids are attached by their kinetochores to microtubules from opposite poles
- 20. prophase •kinetochore is aprotein strucutre on chromatide where microtubules will bind to it in cell division to pull the two sister chromatide a part •each sister chromatid has its own kinetochore (arise from centromer) •sister chromatids become attached by their kinetochores to microtubules from opposite poles •Used in cell division (mitosis & miosis)
- 21. Spindle Fiber attachedto Chromosome 21 Kinetochore Fiber Chromosome
- 22. prometaphase a systemof microtubules, called the mitotic spindle, organizes between the two poles (opposite ends) of the cell each pole has a microtubule organizing center (MTOC) in animals and some other eukaryotes, centrioles are found in the MTOC
- 23. Late Prophase (prometaphase) 23 Nuclear membrane & nucleolus are broken down Chromosomes continue condensing & are clearly visible Spindle fibers called kinetochores attach to the centromere of each chromosome Spindle finishes forming between the poles of the cell
- 24. Review of Prophase 24 Whatthe cell looks like What’s happening
- 25. METAPHASE 1.Chromosomes chromosomes arehighly condensed line up in the middle (meta phase plate) 2.Nuclear envelope is gone (no nucleus) 3.Spindle fibers (on opposite poles) are stretching towards the chromosomes 4- the mitosis checkpoint appears to be here; progress past metaphase is typically prevented until the kinetochores are all attached to microtubules
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- 27. Review of Metaphase 27 Whatthe cell looks like What’s occurring
- 28. Anaphase Occurs rapidly Sister chromatids are pulled apart to opposite poles of the cell by kinetochore fibers the protein tethers at the centromere between the chromatids are broken each former sister chromatid can now be called a chromosome (daughter) 28
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- 30. Anaphase Review 30 What thecell looks like What’s occurring
- 31. Telophase 31 Sister chromatidsat opposite poles Spindle disassembles Nuclear envelope forms around each set of sister chromatids and chromosome condensed Nucleolus reappears CYTOKINESIS occurs (furrow) Chromosomes reappear as chromatin
- 32. Mitosis: telophase prophaseis essentially reversed the mitotic spindle is disintegrated the chromosomes decondense nuclear membranes reform around the genetic material to form two nuclei each has an identical copy of the genetic information nucleoli reappear, and interphase cellular functions resume *
- 33. Comparison of Anaphase& Telophase 33
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- 35. Cell Division inProkaryotes Prokaryotes such as bacteria divide into 2 identical cells by the process of binary fission Single chromosome makes a copy of itself Cell wall forms between the chromosomes dividing the cell 35 Parent cell 2 identical daughter cells Chromosome doubles Cell splits
- 36. What is theCell Cycle? Parent cells are diploid and make 2 daughter cells that are also diploid with their own new nuclei. Diploid means 2 of each chromosome: 2 (n)= 2 (23) = 46 chromosomes It happens in all of your somatic(body) cells in order to get the same DNA inside each cell. (your reproductive cells do something different) I P M A T C I Peed on the MAT, see?
- 38. Figure 12.5-3 Chromosomes Chromosomal DNA molecules Centromere Chromosome arm Chromosomeduplication (including DNA replication) and condensation Sister chromatids Separation of sister chromatids into two chromosomes 1 2 3
- 39. cytokinesis Means divisionof the cytoplasm divides the cell into two daughter cells (cytoplasm, organelles cytokinesis usually begins in telophase and ends shortly thereafter
- 40. Cytokinesis 40 Cleavage furrow in animalcell Cell plate in animal cell
- 41. Daughter Cells ofMitosis 41 Have the same number of chromosomes as each other and as the parent cell from which they were formed Identical to each other, but smaller than parent cell Must grow in size to become mature cells (G1 of Interphase) Ready to enter in new cell cycle
- 42. Identical Daughter Cells 42 Chromosomenumber the same, but cells smaller than parent cell What is the 2n or diploid number? 2
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- 45. Draw & Learnthese Stages 45
- 46. Draw & Learnthese Stages 46
- 47. Name the MitoticStages: 47 Interphase Prophase Metaphase Anaphase Telophase Name this? Name this?
- 48. Uncontrolled Mitosis If mitosisis not controlled, unlimited cell division occurs causing cancerous tumors Oncogenes are special proteins that increase the chance that a normal cell develops into a tumor cell 48 Cancer cells
- 49. controlled Mitosis Thefrequency of cell division varies with the type of cell These differences result from regulation at the molecular level Cancer cells manage to escape the usual controls on the cell cycle © 2011 Pearson Education, Inc.
- 50. The Cell CycleControl System The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock The cell cycle control system is regulated by both internal and external controls The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received © 2011 Pearson Education, Inc.
- 51. G1 checkpoint G1 G2 G2 checkpoint Mcheckpoint M S Control system Figure 12.15
- 52. For manycells, the G1 checkpoint seems to be the most important If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase © 2011 Pearson Education, Inc.
- 53. Figure 12.16 G1 checkpoint G1G1 G0 (a) Cell receives a go-ahead signal. (b) Cell does not receive a go-ahead signal.
- 54. Eukaryotic Cell Cycle cyclinsand cyclin-dependent protein kinases (Cdks) cytokinins; growth factors; suppressors; cancer cells
- 55. Cell Cycle Checkpoints The decision to proceed from one part of the cell cycle to another depends on a variety of factors Growth DNA replication DNA integrity Cellular integrity The mechanisms that the cell has to monitor these factors act at “checkpoints” Generally, the feedback from checkpoints is through negative regulation—sending a signal to stop the progression of the cell cycle rather than dialing back a positive signal. Schematic of Cell Cycle Checkpoints
- 56. Cell Cycle Checkpoints G1 (Restriction) Checkpoint DNA Replication Checkpoint (end of G2) Cell will not proceed with mitosis if DNA replication is not complete Cells with mutations in this checkpoint pathway or cultured mammalian cells treated with caffeine will proceed through mitosis with unreplicated DNA.
- 57. Cell Cycle Arrest Cells have “checkpoints” where they “proof-read” DNA for damage before continuing to cycle. This ensures faithful chromosome replication and maintains genomic integrity. Irradiation causes cells to arrest at these checkpoints Cells tend to arrest at • G1 - especially if they have wt p53. This may lead to apoptosis • Intra S phase - initiation and elongation stages of DNA replication are affected by p53 independent mechanisms • G2 - most cells arrest here - allows chromatid repair prior to segregation in M • M phase - block in anaphase until all sister chromatids have aligned properly on the spindle - Monitors spindle integrity for cytokinesis
- 58. Cell Cycle Checkpoints Growth checkpoints In budding yeasts, division produces a small daughter cell and a large mother cell. The daughter cell spends a longer time growing in G1 before it can divide again. There is a minimum size that must be reached before S phase can begin. In animal cells, external growth factors play a major role in providing signals about cell growth and differentiation and regulating the cell cycle.
- 59. Cell Cycle Checkpoints Spindle-attachment checkpoint Before anaphase (separation of chromosomes) there is a checkpoint to ensure the chromatids are correctly attached to the mitotic spindle The kinetochore (where the chromatids attach to the spindle) is the structure that is monitored
- 60. Cell Cycle Checkpoints Exiting Mitosis Degradation of the M phase cyclin/cdk complex (aka MPF) is required to proceed with the final activities of mitosis (spindle disassembly and formation of the nuclear envelopes). This degradation is accomplished by ubiquitinylation of the complex. The cdc20-APC complex is responsible for signaling the degradation and exit from mitosis.
- 61. Loss of CellCycle Controls in Cancer Cells Cancer cells do not respond normally to the body’s control mechanisms Cancer cells may not need growth factors to grow and divide They may make their own growth factor They may convey a growth factor’s signal without the presence of the growth factor They may have an abnormal cell cycle control system © 2011 Pearson Education, Inc.