CELL CYCLE , MITOSIS ,MEIOSIS AND CELL REGULATION

CELL CYCLE ,MITOSIS , MEIOSIS AND CELL REGULATION

1. CELL CYCLE AND REGULATION

2. CONTENTS CELL CYLCE PHASES OF CELL CYCLE MITOSIS MEIOSIS CELL REGULATION

3. CELL CYCLE very important processes in all living organisms During the cell division, DNA replication and cell growth takes place “The sequence of events by which a cell duplicates its genome, synthesizes the other constituents of the cell and eventually divides into two daughter cells is termed as cell cycle” “Rudolf Virchow ” suggested “ omnis cellula e cellula ” means every cell is derived from pre- existing cells. The duration of the cell cycle varies greatly from one cell type to another cell

4. CELL CYCLE A single-celled yeast can divide every 90-120minutes While a mammalian liver cell divides on average less than once a year Muscle cells, nerve cells, and RBC are the only cells in our body which do not divide Before discussion about cell division first we should know the following terms

5. Cell cycle CHROMATIN: DNA coiled around histone proteins CHROMATID: one half of a duplicated chromosome CHROMOSOME: are two chromatids together , made of condensed chromatin  

6. CENTROMERE the constriction region that divide the chromosome into two chromatids primary constriction of the condensed chromosome clearly visible with a light microscope made up of highly repetitive condensed AT rich, heterchromatic DNA with non- histone proteins cannot bind with microtubules themselves it is the site for kinetochore assembly it ensures delivery of one copy of each chromosome to each daughter at cell division

7. kinetochore Kinetochores are disc shaped protein complexes intimately associated with centromere Kinetochore can only be seen using electron microscope It is the site of assembly and disassembly of microtubules Made of multiple proteins

8. kinetochore It has a trilaminar structure the inner layer is in close contact with condensed centromeric heterochromatin microtubules are attached to the outer layer Made up of specialized types of histones like CENP-A Attachment site for spindle microtubule Involved in the movement of chromosomes during mitosis and meiosis

9. CELL DIVISION IN PROKARYOTES By binary fusion

10. CELL DIVISION IN EUKARYOTES A typical eukaryotic cell cycle is classified into two phases 1. interphase 2. M phase

11. INTERPHASE It is a long, metabolically active phase between two successive mitotic cell division, it has three sub stages Approximately 95% of the cell cycle is spent in interphase

12. G1 PHASE The period between the end of M phase and the start of DNA replication Last for about 11 hours Cell is metabolically active and continuously grows Do not replicate its DNA Raw materials ( enzymes,ATP ) required for the S phase synthesized Increase in cell size

13. S PHASE Also called synthesis phase Period during which DNA replication takes place The amount of DNA per cell divides from 2C to 4C But the number of chromosome remains same i.e., 2N In animals, centriole also divides in cytoplasm but not in plants due to the absence of centriole

14. G2 PHASE The gap period between the DNA replication and the initiation of M phase The synthesis of proteins required for the synthesis of spindle fibres takes place Cell growth continues ATP synthesis increases Synthesis of plasma membrane proteins takes place  

15. G0 STAGE Also called “quiescent stage or inactive stage” Cells that do not divide and exit G phase and enter an inactive stage called Go stage Cells at this stage remain metabolically active but do not proliferate Cells are able to enter reversible or irreversible Go stage

16. Go stage Quiescent state represent a reversible resting stage, cells in this stage remain metabolically active and do not proliferate unless depending on the requirement Senescent cells are dysfunctional cells that have ceased proliferation and are permanently withdraw from the cell cycle Terminally differentiated cells(muscle cells and nerve cell) are those cells that in the course of acquiring specialized functions, have irreversibly lost its ability to proliferate

17. M PHASE mitotic phase It is a short phase It includes two important processes that occur simultaneously they are karyokinesis (division of the nucleus) and cytokinesis (division of the cytoplasm) resulting in two daughter cells After M phase the cell may enter interphase to repeat the cell division or Go phase to arrest the cell cycle

18. M PHASE Two transient cytoskeletol structures that mediate M phase in animal cells. Mitotic spindle assembles first to separate the chromosome Contractile ring ( actin and myosin filaments) assembles to divide the cell in two

19. MITOSIS It was first observed by strasburger in plant cells and Boveri and Flemming in animal cells It is a type of cell division in which a parental cell produces two similar daughter cells that resembles the parental cells. Also called equational cell division because there is no change in chromosome number Occur in somatic cells of the body , so it is also called somatic cell division Mitosis occurs in two stages i.e 1.karyokinesis 2. Cytokinesis

20. KARYOKINESIS: It is the division of nuclear material , it occurs in four stages as follows 1.PROPHASE: It is the longest phase Chromatin begins to condense and becomes visible in light microscope as chromosomes Centrioles move towards the opposite poles Spindle apparatus begin to appear

21. PROMETAPHASE: Starts with the breakdown of the nuclear membrane Chromosome can now attach to spindle microtubules via their kinetochores , and undergo active movement Nucleolus disappear Chromosome are set free in the cytoplasm

22. they are three classes of microtubules in a mitotic spindle 1.kinetochore microtubule: which attach to the kinetochore region of the chromosome 2.polar microtubules: microtubules do not interact with the chromosomes but overlap with polar microtubules from the opposite pole 3.unattached microtubules : which are unattached and are free

23. METAPHASE: Spindle fibres are completely formed The chromosome become short and thick with two distinct chromatids each All the chromosome move towards the centre of the cell and arrange in the equatorial plane to form metsphasic plate Chromosomes are attached to spindle fibres at their kinetochore region

24. ANAPHASE: The paired chromatids separate to form two daughter chromosomes Daughter chromosomes are pulled towards the pole Chromosome number changes from 2N to 4N (due to the separation of chromatids )

25. TELOPHASE: The daughter chromosome reach the opposite poles Nucleolus and nuclear membrane reappears The spindle fibres disappear CYTOKINESIS: It is the division of protoplasm into two daughter cells after karyokinesis The contractile ring ( actin and myosin filament) assembles to divide the cell into two cells In plant cells, cell wall formation begins in the centre and grow outwards In some organisms karyokinesis is not followed by cytokinesis ,leads to the formation of syncytium (liquid endosperm in coconut) Membrane bound organelles are usully present in large number and will be safely inherited , but other organelles like golgi complex , ER break up into small fragments during mitosis

26. SIGNIFICANCE OF MITOSIS : It maintains genetic stability with in the population of cells derived from same parental cell It helps the growth and tissue repair It helps in the replacement of dead and worn out cells It is a means of reproduction in lower animals Takes place in somatic cells There is no change in chromosome number so called equational division

27. MEIOSIS The term meiosis was coined by Former and Moore Type of cell division in which the daughter cells receive only half of the original set of chromosome of the parental cell so called reductional division Reduction of chromosome number is done by one round of DNA replication being followed by two rounds of chromosome segregation Occurs only in germinal cells

28. MEIOSIS At the end of meiosis four daughter cells are formed Each of the daughter cell has one half of the number of chromosomes as the parent Male gamete (sperm) and female gamete (ovum) fertilizes to form diploid zygote develops into a individual having diploid numbers of chromosome, so meiosis helps in maintain the constant number of chromosomes

29. INTERPHASE 1: As we already know during interphase the duplication of DNA, centrioles and synthesis of RNA and proteins take place   MEIOSIS I: KARYOKINESIS: PROPHASE I : it is the longest phase of meiosis and divided into 5 sub stages

30. LEPTOTENE The chromatin condenses to form chromosome and visible under light microscope Each chromosome has two chromatids that are not distinctly visible Also called as bouquet stage because the chromosome ends are attached to the inner nuclear envelop and helps in homologous chromosome pairing and synapsis Centriole move towards outer pole Spindle apparatus begin to appear

31. ZYGOTENE Pairing of homologous chromosome takes place called synapsis . The pair is called bivalent Synaptonemal complex is a protein complex that forms between homologous chromosomes The chromosome continues to undergo condensation Centrioles moving towards opposite poles

32. PACHYTENE The chromosome become more short and thick Each bivalent shows four chromatids called tetrad In this stage the exchange of genetic material takes place between the non sister chromatids of homologous chromosome this process is called crossing over Results in genetic recombinations which is responsible for variations

33. DIPLOTENE: The beginning of the diplotene is recognized by the dissolution of the synaptoneimal complex And the chromosome separated at each other except at the sites of crossing over X – shaped structures are called chaismata  

34. DIAKINESIS Terminalisation of chaismata Chromosome is fully condensed At the end nucleolus and nuclear envelop disappears

35. METAPHASE: Spindle fibres are completely formed The chromosome become short and thick with two distinct chromatids each All the chromosome move towards the centre of the cell and arrange in the equatorial plane to form metsphasic plate Chromosomes are attached to spindle fibres at their kinetochore region

36. ANAPHASE: The homologous chromosomes separate, while sister chromatids remain associated at their centromeres  

37. TELOPHASE: The homologous chromosome reach the opposite poles Nucleolus and nuclear membrane reappears The spindle fibres disappear CYTOKINESIS: It is the division of protoplasm into two daughter cells after karyokinesis

38. INTERKINESIS The interphase after the first meiotic division is called interkinesis Or the time gap between the meiosis I and meiosis II Generally it is short or may not occur at all No DNA replication occur during this stage  

39. MEIOSIS II Similar to the normal mitosis There is no S phase The chromatids of each chromosome are no longer identical because of recombination during prophase I of meiosis I

40. SIGNIFICANCE OF MEIOSIS It helps to restore diploidy and maintain the constant number of chromosomes for a species Meiosis produce new combination of chromosomes and genes by crossing over Increases the genetic variations ,important for the process of evolution Reduction of chromosome number so called reductional division

41. MITOSIS MEIOSIS Take place in the somatic cells of the body Take place in the germ cells Occurs in both sexually as well as asexually reproducing organisms Occurs only in sexual reproducing organisms The cell divide only once There are two cell divisions the first and the second meiotic division Interphase occur prior to each division Interphase preceeds only in meiosis 1. It does not occur prior in meiosis II DNA replication takes place during interphase I DNA replication takes place during interphase I but not interphase II The duration of prophase is short usually of a few hours Prophase is comparatively longer and may take days Prophase is comparatively simple Prophase is complicated and divided into leptotene,zygotene , pachytene , diplotene , and diakinesis . DIFFERENCE BETWEEN MITOSIS AND MEIOSIS:

42. The cell divides only once and the chromosome also divide only once There is no synapsis There are two cell divisions but the chromosome divide only once Synapsis of homologous chromosome take place during prophase The two chromatids of a chromosome do not exchange segments during prophase Chromatids of two homologous chromosome exchange segments during crossing over The arms of the prophase chromatids are close to one another The arms of the chromatids are separated widely in prophase II Chromosomes are already duplicated at the beginning of prophase When prophase I commences the chromosomes appear single,(although DNA replication taken place in interphase I) No bouguet stage is recorded Chromosome of animals and some plants show convergence towards one side during early prophase I it is known as bouquet stage A synaptionemal complex is absent Synapsed homologous chromosome develop a synaptionemal complex Crossing over is absent Crossing over or exchange of similar segments between non sister chromatids of homologous chromosomes usually take place during pachytene stage

43. Chiasmata are absent Chiasmata or visible connections between homologous chromosomes of bivalents are observed during diplotene, diakinesis (prophase I) and metaphase I In the metaphase plate all the centromeres line up in same plate In metaphase I the centromers are lined up in two planes which are parallel to one other The metaphase plate is made up of chromosome pairs The metaphase plate is made up of paired chromosome pairs Two chromatids of a chromosome are genetically similar The genetic constitution of the daughter cells is identical to that of the parent cells Two chromatids of chromosome are often genetically different due to the crossing over The genetic constitution of the daughter cells differs from that of the parent cells. The chromosome of daughter cells usually contain a mixture of maternal and paternal genes Division of the centromeres take place during anaphase There is no centromeric division during anaphase I centromeres divide only during anaphase II The chromosome seperates simulta- neously during anaphase Short chromosomes seperates early, separation of long chromosome is delayed Anaphase chromosome are single stranded Chromosomes are double stranded in anaphase I. but single stranded in anaphase II Similar chromosome move towards the opposite poles in anaphase Dissimilar chromosomes move towards the opposite poles both in anaphase I and II

44. Spindle fibers disappear completely in telophase Spindle fibers do not disappear completely in telophase I nucleoli reappear at telophase nucleoli do not reappear at telophase cytokinesis follows every mitosis. It produces two new cells cytokinesis often does not occur after the first or reduction division. It is often simultaneously after second division to result in four cells The chromosome number remains constant at the end of mitosis the chromosome number is reduced from the diploid to the haploid it helps in multiplication of cells multiplication of cells is not involved Take part in healing and repair Take part in the formation of gametes and maintainance of chromosome number of the race

45. CELL CYCLE REGULATION

46. CELL CYCLE CHECKPOINTS A checkpoint is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cycle can be halted until conditions are favorable.

47. G 1 CHECKPOINT Damage to DNA external factors are evaluated at the G1 checkpoint Nutrient availability if conditions are inadequate, the cell will not be allowed to continue to the S phase of interphase .

48. G 2 CHECKPOINT The G2 checkpoint ensures all of the chromosomes have been replicated and that the replicated DNA is not damaged before cell enters mitosis.

49. M CHECKPOINT The M checkpoint determines whether all the sister chromatids are correctly attached to the spindle microtubules before the cell enters the irreversible anaphase stage.

50. Cell cycle control system the engine that drives the progression from one step of the cell cycle to the next are a series of protein complexes composed of two subunits 1.cyclins 2.cyclin dependent protein kinase Cyclin is a regulatory component , CDK is catalytic and acts as protein kinase

51. CYCLINS Named because they undergo a cycle of synthesis and degradation in each cell cycle Four classses of cyclins 1.G1-cyclins 2.G1/S- cyclins 3.S-cyclins 4.M-cyclins

52. CYCLIN-DEPENDENT KINASE A family of functionally related protein kinases Add phosphate groups to target substrate Named so because their activity are regulated by cyclins The target protein for CDK phosphorylation are determined by the associated cyclins because different cyclins are present at different phases of the cycle

53. Cyclin dependent kinases CDK 4 and CDK6 only partner with D-type cyclins CDK 1 and CDK 2 bind to multiple cyclins (A,B,D,E) Cyclin E-CDK2 triggers S phase Cyclins D and CDK 4 and CDK 6 regulate events in early G1 phase Cyclin A-CDK 2 and cyclin A-CDK1 regulate the completion of S phase and Cyclin B-CDK 1 is responsible for M phase

54. Regulation of activity of M-CDK complex 1.interaction of mitotic cyclin with CDK form complex 2.the CDK subunit can be phosphorylated at two regulatory sites by Wee 1 at tyrosine-15 and by CAK at threonine -161 When both residues are phosphorylated M-CDK is inactive Finally removal of the phosphate from tyrosine-15 by cdc25 phosphatase yeilds active M-CDK complex

55. INHIBITORS

56. DNA damage checkpoints ATM and ATR activated when any damaged or unreplicated DNA is present ATM i s activated principally by double stranded breaks and ATR by single stranded or unreplicated break ATM and ATR the phosphorylate and activate the CHK2 and CHK1 CHK1 and CHK2 phosphorylate and inhibit the Cdc25A and Cdc25C( which are required for the activation of Cdk 2 and Cdk1)

57. role of p53 in G1 arrest in response to DNA damage

58. And they are several regulatory pathways 1.cell cycle regulation of Rb and E2F 2.the spindle assembly checkpoint Unattached kinetochores lead to the assembly of a complex of Mad/ Bub protein in which Mad activated and prevent APC activation by inhibiting Cdc20