Molecular Genetics

Cyclin-dependent phosphorylation of proteins is central to coordination of replication and division.

Facts

• In S. cerevisiae and S. pombe, genes (cdc2 and CDC28, respectively) are required for the transition from G1 to S phase. The products of these genes are homologous to a p34 kinase characterized in Xenopus. The genes are also required for the initiation of mitosis.
• p34 kinases are constitutive enzymes, capable of being phosphorylated. There can be several forms in each organism. The kinase activities are activated by binding to proteins of the cyclin family.
• There are multiple cyclins, each with a specific role. Cyclins are unstable. Some are triggered for destruction by phosphorylation. Others are inherently unstable and are synthesized discontinuously during the cell cycle.
• A protein was isolated that would initiate mitosis-like reactions in cell-free extracts. This protein, mitosis-promoting factor (MPF), consisted of p34 kinase and a cyclin. It phosphorylated proteins activating them to cause nuclear breakdown, chromosome condensation, spindle asssembly, histone H1 phosphorylation and cyclin degradation.

Interpretations

• Control of the initiation of S phase and of M phase occurs via a cascade of regulatory events that includes protein phosphorylations.
• Mutations in some genes affect both S phase and M phase initiation (eg. P34) while mutations in others affect only one (eg. M-cyclin).

Further information

• Cyclin-mediated events leading to initiation of DNA synthesis occur considerably before the start of replication.

This is page 1333 of Molecular Genetics by Ulrich Melcher, © 1997, 1998, 1999