Interaction between cdc13+ and cdc2+ in the control of mitosis in fission yeast; dissociation of the G1 and G2 roles of the cdc2+ protein kinase.

Abstract

A cold‐sensitive (cs) allele of cdc2, a gene that acts in both the G1 and G2 phases of the fission yeast cell cycle, has been isolated by classical mutagenesis. Further mutagenesis of a cdc2cs strain yielded an extragenic suppressor that rescued the cs cell cycle defect but simultaneously conferred a temperature‐sensitive (ts) cdc phenotype. This suppressor mutation was shown to be an allele of cdc13, a previously identified gene. A variety of allele‐specific interactions between cdc2 and cdc13 were discovered. These included suppression of cdc13ts alleles by introduction of the cdc2+ gene on a multi‐copy plasmid vector. cdc13+ is required in G2 for mitotic initiation and was shown to play no role in the G1 phase of the cell cycle. cdc2+, however, is essential in G1 for DNA replication and in G2 for mitosis. The newly isolated cs allele of cdc2 that is rescued by a ts allele of cdc13 is defective only in its G2 function. cdc13+ cooperates with cdc2+ in the initiation of mitosis but not in the regulation of DNA replication. We propose that the cdc13+ gene product might be a G2‐specific substrate of the cdc2+ protein kinase.

The Arabidopsis functional homolog of the p34cdc2 protein kinase.

“…For example, a histidine replaces tyrosine at position 97, isoleucine replaces valine at position 11 1, arginine replaces proline at position 228, methionine replaces tyrosine at position 270, and asparagine replaces serine at position 277 (Figure 2). Because the cdc2 gene product physically interacts with other proteins-cyclins (Booher and Beach, 1987;Draetta et al, 1989;Hadwiger et al, 1989;Gautier et al, 1990) and the suc7+ product (Hayles et al, 1986a(Hayles et al, , 1986bBrizuela et al, 1987;Hindley et al, 1987;Dunphy and Newport, 1989;Moreno et al, 1989;Richardson et al, 1990)-to have mitotic kinase activity, it might be possible to define the domains that are required for the interaction (reviewed in Draetta, 1990). Substitutions within these domains could have some degree of tolerance, provided the conformational change in the structure is not to0 drastic.…”

Protein kinases controlling the onset of mitosis

“…Given the high homology between Cdk2 and Cdk1, the model is likely extendable to the latter. The influence of Cdk1 on mitotic entry has been established through genetic studies in model organisms [49][50][51][52][53], microinjection experiments [54,55], expression of a dominant-negative mutant isoform [56], induced expression of cyclin-dependent-kinase inhibitors (CKI) [57,58] and the use of chemical inhibitors (reviewed in [59]) and have been extensively reviewed elsewhere [60]. The mechanisms through which Cdk1 promotes entry and transition through mitosis are multiple and are mediated by phosphorylation of numerous substrates.…”

Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes.

“…Each CDK requires the association of a cyclin that serves as a positive regulatory subunit for the kinase activity. In both budding and fission yeasts, a single catalytic subunit, p34cDc /cDc28, is required for both the G1/S and G2/M transitions through association with either Gl cyclins (CLN-type) or mitotic cyclins (B-type) (Booher and Beach, 1987;Hadwiger et al, 1989;Wittenberg et al, 1990;Bueno et al, 1991;Ghiara et al, 1991;Surana et al, 1991). In vertebrates, whereas p34CDC2 plays an essential role in mitosis (Riabowol et al, 1989; reviewed by Draetta, 1990), the function of p34CDC2 in Gl and S phases appears to be mediated not by a single kinase but by a family of CDC2-related proteins.…”