Molecular event during Cell cycle By KK Sahu Sir
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The document discusses the cell cycle, detailing the processes of cell division, the types of cells, and the molecular events involved. It explores cell phases such as interphase (with G1, S, G2 phases) and M-phase, along with checkpoints that regulate these stages. Key roles of cdc genes and the significance of mitosis in growth, asexual reproduction, and healing are emphasized, concluding with implications for cancer when cell division regulation is disrupted.
Molecular event during Cell cycle By KK Sahu Sir
- 1. MOLECULAR EVENT DURING CELL CYCLE By KAUSHAL KUMAR SAHU Assistant Professor (Ad Hoc) Department of Biotechnology Govt. Digvijay Autonomous P. G. College Raj-Nandgaon ( C. G. )
- 2. SYNOPOSSIS • WHAT IS CELL? • WHAT IS CELL DIVISION OR CELL CYCLE? • WHY DO CELL DIVIDE? • HISTORY • CELL CYCLE INTERPHASE M-PHASE • MOLECULAR EVENT DURING CELL CYCLE AND CELL REGULATION • TYPES OF CELL DIVISION • IMPORTANCE OF CELL DIVISION • ABNORMALTIES OF CELL CYCLE • REFRENCES
- 3. WHAT IS CELL ? • Life exists only in the form of cell. • Cell is a structural and functional unit of living being which consist of a membrane covered mass of protoplasm. • New cell develop from division of pre-existing cells
- 4. TYPES OF CELLS • There are two type of cell : (1)Somatic cell somatic cell make up all the internal organ skin,bone,blood,connective tissue. (2)Germ cell Mammmalian germ cells give rise to spermatozoa and ova which fuse during fertilization to produce a cell called a zygote .
- 6. WHAT IS CELL DIVISION ? • Cell division is the process by which a cell after it replication of its components splits up to form 2-4 cells. • The cell which under goes division is called mother cell while the newly formed cell are called daughter cell.
- 7. WHY DO THE CELL DIVIDE? (1) Minimum growth. (2) Surface volume ratio. (3) Nucleocytoplasmic or kernplasma ratio. (4) Mitogens.
- 8. WHAT IS THE HISTORY OF CELL DIVISION? (1)Prevost and Duman 1824 studied cleavage in the fertilized egg of frog. (2)Rudolf virchow 1855 observed that new cell always from pre-existing cells.omnis cellula-e-cellula. (3)Boveri and Flemming 1879 studied details of somatic cell division. (4)Weismann in 1887 suggested the occurance of a special type of cell division for gamete formation. (5)Van Beneden, sutton, winiwater studied details of double division required forformalion of gamates.
- 9. CELL CYCLE • It is an oderly series of changes that occures in a cell by which it duplicates its content and divides into two. • The period required to complete one cell cycle is called generation time. • It was studied by Howard and Pelc 1953. • It is consist of two phase: (1)Interphase. (2)M-phase.
- 11. INTERPHASE • It is interval between two successive division of a eukaryotic cell in which growth and synthetic activities prepare a cell and its nucleus to divide again. • It is non-dividing phase. • The change are not externally apperent so that previously interphase was also called resting phase.
- 12. STAGE OF INTERPHASE • It has three stages: (1) G1-phase. (2) S-phase. (3) G2-phase.
- 13. G1-PHASE • G1-phase occurs immediately after the previous division. • G1 is also called gap1 or First growth phase. • Cell size increase. • Nucleus also grow but to smaller extent. • Synthesis of new proteins and RNA needed for various activities of growing cell also occurs in this phase. • Mitochondria , chloroplast , golgi body , ribosome etc are formed in this phase.
- 14. G0-PHASE • It was first discovered by Laytha 1963. • It is noncycling state of cell which leaves the cell cycle to the early half of G1-phase due to absence of cycling factors and activation of certain gene. • Cell size and shape become specific. • Somatic cell in the body of an individual are in G0- phase.
- 15. S-PHASE • It is synthetic phase in which DNA molecule replicate. • Histone protein are formed from their precursor. • Along with DNA , they from nuclesomes that are basic to formation of chromatic threads. • At the end of S-phase each chromosome two chromatids that are attached to each other in the region of their centromeres. • Chromosome is changed from single standard form to two standard ie. From monad to dyad.
- 16. G2-PHASE • It is second growth phase, also called Gap2 or post synthetic phase. • Cell size increase. • Nucleus grow in size. • Energy store increase. • There is again an intensive formation of biochemicals including RNA’S and protein. • Bio chemicals are formed for spindle and other structure connected with cell division.
- 17. M-PHASE • It is phase of cell division . • Division may occur by mitosis or meiosis. • M-phase seprate the products of chromosome replication and distributes the same equitably into two daughter cell. • There is also distribution of cell organelles and cytoplasm. • M-phase consist of two processes: (1)karyokinesis. (2)Cytokinesis.
- 19. Duration of cell cycle • The duration of cell cycle varies from 25-30 hours in different cells. • In E.coli the cell cycle is completed in 20 minutes. • In root tip of onion 20 hours . • In human it is completed in 24 hours. (1)1.45 hours for M-phase. (2)8.15 hours for G1-phase. (3)8 hours for S-phase. (4)6 hours for G2-phase.
- 20. DURATION OF CELL CYCLE
- 21. MOLECULAE EVENT TAKE PLACE DURING REGULATION OF CELL CYCLE. • A cell must ensure the following before entering cell division: (1)Almost doubling of cell mass. (2) Every DNA sequence present in cell nucleus is replicated once and only once. (3) Absence of DNA damage , especially double stand breaks.
- 22. A DIAGRAMMATIC SUMMARY OF THE CHANGES IN CELL MASS AND DNA CONTENT DURING CELL CYCLE PROTEIN AND RNA *1 *2 4C 4C 2C 2C G1 S G2 M
- 23. DOMINO AND CLOCK THEORIES According to this theory cell division is comparable to biosynthetic pathways in which a given reaction can occur only when the previous reaction in the pathway is successfully completed. In this scheme, specific regulators that either activate or inhibit specific stage of cell division . This theory was developed from ananlysis of cdc.(cell division cycle) and the concept of checkpoint is intergral to it.
- 24. CHECKPOINTS • A checkpoint is a specific point in cell cycle at which cell evalute whether all the condition necessary for cell division are fullfilled. • There are two major checkpoint in eukarytoes: (1)START or restriction point . (2)Initiation of M-phase.
- 25. START or restriction point • At this checkpoint , a cell evalutes its internal as well as external environment and assesses if, it is in a position to enter S-phase. • If it find the condition to be suitable ,it decides to enter S-phase begin . • This checkpoint is regulated by a protein kinase that is similar to M-phase kinase.
- 27. INITIATION OF M-PHASE • The second checkpoint is located towards the end of G2 phase. • At this checkpoint , a cell evalutes doubling of its cell mass and the completeness of DNA replication and absence of DNA damage. • This checkpoint is the main control point in haploid organism .
- 28. CELL DIVISON CYCLE GENES (cdc gene) • Those genes whose products are required specifically for cell cycle to proceed normally are called cell division cycle (cdc gene). • A mutation in a cdc gene block cell cycle at a specific stage. • Function: (1)They are needed for structural purpose. Example:enzyme of DNA replication. (2)They are involved in the regulation of cell cycle.
- 29. FACTOR REGULATION M-PHASE INITIATION • The entry of cell into S-phase and M-phase is regulated by specific activators which are protein kinase. • Evedience to prove it: (1)Animal cell heterokaryons . Heterokaryons are produced by fusing two or more cells with help of usually , PEG (polyethylene glycol).
- 31. conclusion • An activator present in S-phase cells induces G1 cell to enter S-phase. However this activation has no effect on G2 phase nuclei. • An activator present in M-phase cell induces G1, S , G2 nuclei to enter M-phase.
- 32. MATURATION PROMOTING FACTOR • Immature oocytes of xenopus are arrested at start of meiosis that is equivalent to G2 phase of mitosis. • When cytoplasm from egg is injected into immature oocytes the later are induced and undergo maturation. • Therefore the factor present in egg cytoplasm that induces the maturation of oocytes was called maturation promoting factor or MPF.
- 33. M-PHASE KINASE • MPF (maturation promoting factor) also induces somatic cell to enter M-phase therefore it is called M-phase promoting factor. • MPF has two subunit designated as: (1)p34 (catalytic subunit). (2)p45 (regulatory subunit).
- 34. CATALYTIC SUBUNITS • The catalytic subunit is so called because it carries out phosphorylation of target protein. • A protein kinase is an enzyme that catalyzes phosphorylation of protein. • In xenopus frog and mammals this subunit is known as CDC28. • The level of p34 remain constant throughout the cell cycle and is in excess of p45. • During interphase the catalysic subunit is present in inactive form toward the end of G2 phase.
- 35. KINASE THAT REGULATE ENTRY OF CELLS INTO M-PHASE AND S-PHASE BY CATALYTIC SUBUNITS ORGANISM M-PHAES KINASE PROTEIN KINASE REGULATING THE ONSET OF S-PHASE MAMMALS,FROGS p34 CDK2 and CDK4 S.Cereisiae CDC28 CDC28 S.Prombe Cdc2 Cdc2
- 36. REGULATORY SUBUNIT • The subunit p45 function as the regulatory subunit of M- phase kinase in mammals and frogs. • This subunit is essential for the catalytic action of p45, and allow specific target proteins. • Regulatory subunit is commonly called as cyclin. • P45 is degraded abruptly by proteolysis during early M- phase. • Cyclin destruction during mitosis eliminates M-phase kinase activity, this is essential for the cell to exist M- phase.
- 37. THE KINASE THAT REGULATE ENTRY OF CELL INTO M- PHASE AND S-PHASE BY REGULATORY SUBUNIT ORGANISM M-PHASE KINASE PROTEIN KINASE REGULATUNG THE ONSET OF S-PHASE MAMMALS, FROGS Cyclins A, B1, B2 Cyclins A, C, D1, D2, D3, E S.cerevisiae CLB1-CLB4 CLNI-CLN3 S.Pombe Cdc 13 Cig2
- 38. They are of two types: (1) G2 cyclins: component of M-phase kinase, cyclins A, B1 and B2 in animals, Cdc 13 in S.pombe, CLBi-4 in S.cerevisiae. Gradual accumulation-abrupt proteoiytic degradatio. (2)G1 cyclins: Component of the kinase regulating onset of S-phase, cyclins A, C, D1-3 and E in animals,Cig2 in S.pombe, CLNi-3 in S.cereivsiae. Enhanced transcription rate.
- 39. ACTIVATION /INACTIVATION OF M-PHASE KINASE In case of mammals and frogs, activation and inactivation of M-phase kinase invovles the following: (1)Phosphroylation of certain amino acid. (2) Dephosphorylation of certain other amino acids. (3) Proteolytic destruction of cyclins.
- 40. M PHASE KINASE :ACTIVATION • Accumulation as p34 – p45 dimer in an inactive form. • Inactive form has P at Thr-14 and Tyr-15 of p34. • Activation occurs towards the end of G2 phase by two events: (1) Dephosphorylation:l removal of P from Thr-14 and Try-15. (2) Phosphorylation : Thr-161 is phosphorylated. (3) Activated kinase induces M phase.
- 41. INACTIVATION • During M phase , inactivation is achieved by proteolysis of p45. • P34 is now present as monomer. • Inactivation is reinforced by: (1) Dephosphorylation : Thr-161 is dephosphorylated. (2) Phosphorylation:unphosphorylated p34 associates with p45 to form inactive dimer; Thr-14 and Tyr-15 are now phosphorylated.
- 42. CYCLIN ACTIVATION AND INACTIVATION Thr Tyr Thr dephosphorlation Thr tyr Thr-161 cyclin phosphorlation phosphorylation ACTIVE M PHASE KINASE cyclin proteoiysis thr14 Tyr15 Thr161 Thr Tyr Thr161 p phosphorylation cyclin synthesis (Thr14, Tyr 15 after start) dephosphorylation P34 cycl in p p p p34 cycli n p34 cycl in p34 p34 p34 cycli n p p p p p p cycli n
- 45. TYPES OF CELL DIVISION
- 46. TYPE OF CELL DIVISION • MITOSIS: • Mitosis is a mode of cell division in which daughter cell are genetically similar to the mother cell because their nuclei come to have the same number and type of chromosomes as are present in daughter cell. • It is also called somatic cell division. OCCURANCE: • It occurs in almost all cell during growth of embryo.later on it occur in some specific region like skin, bone marrow.
- 47. KARYOKINESIS • The division of nucleus is called karyokinesis. • It is completed in following two phase: (1) interphase;. (2) M-phase. prophase metaphase anaphase telophase
- 49. PROPHASE • PROSPHASE IS THE FIRST STAGE AND LONGEST OF the four phase • Chromatin of the nucleus become condensed forming chromosomes. • Chromosome replication occurs in prophase.each chromosome is consist of two chromatids. • Nuclear membrane and nucleolus dissaper at late prophase. • Centriole divides into two.from each centriole arise radiating fibres giving the apperance of star called astar. • Two astar are known as amphiaster.
- 51. METAPHASE • Chromosomes under maximum condensation and occupy the center of the cell forming an equqtorial plate. • The centromeres of a chromosome are attached to the spindle fibres. • During metaphase fibres of spindle apparatus are made of microtubules of three type: (1) Kinetochroe microtubules (2) Polar microtubules (3) Aster microtubules.
- 53. ANAPHASE • During anaphase, separation of chromatids take place, the chromatides move in opposite direction towards the poles. • Spindle fibres contract in anaphase. • Anaphase is the shortest phase in duration.
- 55. TELOPHASE • The chromosome form the chromatin network. the nuclear membrane and nucleolus reappear. • Telophase result in the formation of two daughter nuclei identical in number of chromosomes and amount of DNA.
- 57. CYTOKINESIS • CYTOKINESIS is the division of cytoplasm . • In case of animal cells ,cytokinesis takes place through cell furrow. • Cytokinesis take place in plant by the formation of cell plate. • Cell wall is formed cell plate which is also referred to as phragmoplast.
- 59. SIGNIFICANCE OF MITOSIS • Mitosis is the type of cell division which takes place for growth of an organism. • Mitosis is the basis of asexual reproduction. • The major significance of mitosis is production of genetically identical cells.
- 60. MICELLANEOUS POINT • Colchicine, an alkaloid from the autumn crocus interferes with the spindle formation. • Colchicine is known as a mitotic poison; it arrests cell division at metaphase. • A temporary suppression of cell division activity in cell population can be brought about by colchicine treatment. • In endomitosis chromosomes duplicated but the nucleus does not divide.
- 61. CANCER • CANCER is a disease in which the regulation of cell cycle is disrupted. • In cancer cells mitotic cell division occurs continuously and more rapidly than in normal cells. • Four type of keys that are responsible for the cell division process: (1) Oncogenes tell cell where to divide. (2) Tumor suppressor gene tell cells when not to divide. (3) Suicide gene control apoptosis and tell the cell to kill itself if something goes wrong.
- 62. TUMOUR
- 64. IMPORTANCE OF CELL DIVISION (1) NEW INDIVIDUAL: each new individual begin its life as a new single cell, commonly the fertilized egg or zygote. (2) GROWTH: all multicellular organism are formed by reapeted division of single cell. (3) REPLACEMENT: damaged cell are being continously replaced . (4) HEALING: an injury of healed through formation of new cell.
- 65. REFRANCES • GERALD KARP- 6th EDITION • FUNDMENTALS OF GENETICS. • GRB Dr.R K PILLAI • S.P JAIN 8th EDITION • IMAGES FROM INTERNET.