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)

QuickTime™ and aSorenson Video decompressorare needed to see this picture.

QuickTime™ and aVideo decompressor

are needed to see this picture.

• 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 experimentJohnson and Rao 1971

G1 M M S M M G2 M M

• 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

Generation of temperature sensitive budding yeast mutants

Analysis of ts cell cycle mutants

G1S

M MM 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 cyclin2. Inhibitory phosphorylation3. Activating phosophorylation4. Binding of CKI5. Cellular localization