Checkpoints couple transcription network oscillator dynamics to cell-cycle progression.

Journal Article

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.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.Our findings indicate that checkpoint mechanisms, likely via phosphorylation of network transcription factors, maintain coupling of the network oscillator to progression during cell-cycle arrest.

Full Text

Duke Authors

Cited Authors

  • Bristow, SL; Leman, AR; Simmons Kovacs, LA; Deckard, A; Harer, J; Haase, SB

Published Date

  • September 5, 2014

Published In

Volume / Issue

  • 15 / 9

Start / End Page

  • 446 -

PubMed ID

  • 25200947

Electronic International Standard Serial Number (EISSN)

  • 1474-760X

International Standard Serial Number (ISSN)

  • 1474-7596

Digital Object Identifier (DOI)

  • 10.1186/preaccept-1107846495134380

Language

  • eng