Summary During embryonic cell cycles, B-cyclin-CDKs function as the core component of an autonomous oscillator. Current models for the cell-cycle oscillator in non-embryonic cells are slightly more complex, incorporating multiple G1, S-phase, and mitotic cyclin-CDK complexes. However, periodic events persist in yeast cells lacking all S-phase and mitotic B-cyclin genes, challenging the assertion that cyclin-CDK complexes are essential for oscillations. These and other results led to the proposal that a network of sequentially activated transcription factors functions as an underlying cell-cycle oscillator. Here we examine the individual contributions of a transcription-factor network and cyclin-CDKs to the maintenance of cell-cycle oscillations. Our findings suggest that while cyclin-CDKs are not required for oscillations, they do contribute to oscillation robustness. A model emerges in which cyclin expression (thereby, CDK activity) is entrained to an autonomous transcriptional oscillator. CDKs then modulate oscillator function and serve as effectors of the oscillator.

In our mathematical model of a transcription factor network, we inadvertently reported the wrong logic rules for the TF, YHP1 in Figure 3A. In each column (A-D), the logic should read, ''MCM1 n SBF n HCM1 ^: ASH1'' (instead of ''n : ASH1''). Note also that activation edges from MCM and HCM1 to YHP1 were unintentionally omitted from the network graphs depicted in Figures 2J and S2A. Finally, in Figure 3C, the distributions for the attractors using activation logic ''D'' should be 35.94%, 64.06%, and 0.00%, respectively, for the attractors 1, 2, and 3.The updated versions of the figures are provided below. We apologize for any confusion these errors may have caused.

Background: The coupling of cyclin dependent kinases (CDKs) to an intrinsically oscillating network of transcription factors has been proposed to control progression through the cell cycle in budding yeast, Saccharomyces cerevisiae. The transcription network regulates the temporal expression of many genes, including cyclins, and drives cell-cycle progression, in part, by generating successive waves of distinct CDK activities that trigger the ordered program of cell-cycle events. Network oscillations continue autonomously in mutant cells arrested by depletion of CDK activities, suggesting the oscillator can be uncoupled from cell-cycle progression. It is not clear what mechanisms, if any, ensure that the network oscillator is restrained when progression in normal cells is delayed or arrested. A recent proposal suggests CDK acts as a master regulator of cell-cycle processes that have the potential for autonomous oscillatory behavior. Results: Here we find that mitotic CDK is not sufficient for fully inhibiting transcript oscillations in arrested cells. We do find that activation of the DNA replication and spindle assembly checkpoints can fully arrest the network oscillator via overlapping but distinct mechanisms. Further, we demonstrate that the DNA replication checkpoint effector protein, Rad53, acts to arrest a portion of transcript oscillations in addition to its role in halting cell-cycle progression.