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The wonderful duplicating “machine” A briefe history of the cell cycle 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase (Howard.

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Presentation on theme: "The wonderful duplicating “machine” A briefe history of the cell cycle 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase (Howard."— Presentation transcript:

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2 The wonderful duplicating “machine”

3 A briefe history of the cell cycle 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase (Howard and Pelc) 1970 Cell fusion experiments (Rao and Johnson) 1971 Discovery of MPF (Masui and Markert) 197x Yeast cdc mutants (Nurse, Hartwell etc.) 1983 Discovery of the first cyclins (Hunt) 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)

4 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase (Howard and Pelc) 1970 Cell fusion experiments (Rao and Johnson) 1971 Discovery of MPF (Masui and Markert) 197x Yeast cdc mutants (Nurse, Hartwell etc.) 1983 Discovery of the first cyclins (Hunt) 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)

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11 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase (Howard and Pelc) 1970 Cell fusion experiments (Rao and Johnson) 1971 Discovery of MPF (Masui and Markert) 197x Yeast cdc mutants (Nurse, Hartwell etc.) 1983 Discovery of the first cyclins (Hunt) 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)

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16 Fluorescent Activated Cell Scan/Sorter (FACS)

17 A typical FACS analysis

18 Methods for cell synchronisation

19 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase () 1970 Cell fusion experiments (Rao and Johnson) 1971 Discovery of MPF (Masui and Markert) 197x Yeast cdc mutants (Nurse, Hartwell etc.) 1983 Discovery of the first cyclins (Hunt) 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)

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22 Cell fusion experiment Johnson and Rao 1971 G1MM SMMG2MM

23 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase (Howard and Pelc) 1970 Cell fusion experiments (Rao and Johnson) 1971 Discovery of MPF (Masui and Markert) 197x Yeast cdc mutants (Nurse, Hartwell etc.) 1983 Discovery of the first cyclins (Hunt) 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)

24 Maturation promoting factor cytostatic factor

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26 Discovery of MPF Masui and Markert 1971

27 Oscillations of MPF

28 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase (Howard and Pelc) 1970 Cell fusion experiments (Rao and Johnson) 1971 Discovery of MPF (Masui and Markert) 197x Yeast cdc mutants (Nurse, Hartwell etc.) 1983 Discovery of the first cyclins (Hunt) 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)

29 Model organisms I - Budding yeast (S.cerevisiae) L. Hartwell

30 Model organisms II - Fission yeast (S.pombe) P. Nurse

31 Generation of temperature sensitive budding yeast mutants

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33 Analysis of ts cell cycle mutants G1 S M M M M

34 Identification of cell cycle ts mutants

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37 Some ts mutants which became famous

38 The two models of cell cycle regulation

39 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase (Howard and Pelc) 1970 Cell fusion experiments (Rao and Johnson) 1971 Discovery of MPF (Masui and Markert) 197x Yeast cdc mutants (Nurse, Hartwell etc.) 1983 Discovery of the first cyclins (Hunt) 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)

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42 18xx Interphase-Mitosis (Flemming) 1951 Discovery of a distinct S-phase (Howard and Pelc) 1970 Cell fusion experiments (Rao and Johnson) 1971 Discovery of MPF (Masui and Markert) 197x Yeast cdc mutants (Nurse, Hartwell etc.) 1983 Discovery of the first cyclins (Hunt) 1988 Cyclin B+cdc2 = MPF (Maller, Newport, Beach)

43 Oscillations of mitotic cyclins are required for MPF activity

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45 Regulation of mitotic cyclin levels in cycling cells

46 Cdc2/28 (=cdk1) is regulated by: 1. Binding of a cyclin 2. Inhibitory phosphorylation 3. Activating phosophorylation 4. Binding of CKI 5. Cellular localization

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