Figure 2.

Roles of KRPs and SMRs in the mitotic and endoreplication cell cycles. (A) During mitosis, a feedback loop including KRPs that establishes the 2 alternative states of no CDK activity during G1, and increased CDK activity triggering S phase. SMRs are proposed to restrict S phase CDK activity after the initiation of S phase to prevent premature entry in mitosis, which depends on CDK phosphorylation of G2/M transcription factors. (B) During endoreplication, the cyclical inhibition of CDK activity by KRPs continues unchanged, resulting in cycles of DNA replication. Increased expression of SIM or other SMRs prevents activation of G2/M transcription factors by S phase CDKs, and inhibits any M phase CDKs that are synthesized, thus preventing mitosis. Proposed requirement for SIM or SMRs to be activated via phosphorylation by CYCD/CDKA complexes introduces a time delay that allows initiation of S-phase, but results in inhibition of these complexes before they can contribute to activation of M-phase.