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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The wonderful duplicating “machine”

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)

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)

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)

Fluorescent Activated Cell Scan/Sorter (FACS)

A typical FACS analysis

Methods for cell synchronisation

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)

Cell fusion experiment Johnson and Rao 1971 G1MM SMMG2MM

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)

Maturation promoting factor cytostatic factor

Discovery of MPF Masui and Markert 1971

Oscillations of MPF

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)

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

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

Generation of temperature sensitive budding yeast mutants

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

Identification of cell cycle ts mutants

Some ts mutants which became famous

The two models of cell cycle regulation

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)

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)

Oscillations of mitotic cyclins are required for MPF activity

Regulation of mitotic cyclin levels in cycling cells

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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