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Whenever biological parameters or external conditions change such that a threshold is crossed, the system abruptly switches between different cell cycle states. Experimental studies have uncovered mechanisms that can make the shape of the bistable response curve change dynamically in time. Here, we show how such a dynamically changing bistable switch can provide a cell with better control over the timing of cell cycle transitions. Moreover, cell cycle oscillations built on bistable switches are more robust when the bistability is modulated in time. Our results are not specific to cell cycle models and may apply to other bistable systems in which the bistable response curve is time-dependent.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008231","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T18:49:44Z","timestamp":1610045384000},"page":"e1008231","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":40,"title":["Dynamic bistable switches enhance robustness and accuracy of cell cycle transitions"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4135-0771","authenticated-orcid":true,"given":"Jan","family":"Rombouts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-9561","authenticated-orcid":true,"given":"Lendert","family":"Gelens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"pcbi.1008231.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-environ-102511-084654","article-title":"Environmental Tipping Points","volume":"38","author":"T Lenton","year":"2013","journal-title":"Annual Review of Environments and Resources"},{"issue":"3","key":"pcbi.1008231.ref002","doi-asserted-by":"crossref","first-page":"033501","DOI":"10.1063\/1.5027718","article-title":"Multistability and tipping: From mathematics and physics to climate and brain\u2014Minireview and preface to the focus issue","volume":"28","author":"U Feudel","year":"2018","journal-title":"Chaos: An Interdisciplinary Journal of Nonlinear Science"},{"issue":"2124","key":"pcbi.1008231.ref003","doi-asserted-by":"crossref","first-page":"20170376","DOI":"10.1098\/rsta.2017.0376","article-title":"Dissipative structures in biological systems: bistability, oscillations, spatial patterns and waves","volume":"376","author":"A Goldbeter","year":"2018","journal-title":"Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences"},{"issue":"6976","key":"pcbi.1008231.ref004","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nature02298","article-title":"Multistability in the lactose utilization network of Escherichia coli","volume":"427","author":"EM Ozbudak","year":"2004","journal-title":"Nature"},{"issue":"1","key":"pcbi.1008231.ref005","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cels.2016.01.003","article-title":"Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches","volume":"2","author":"KM Byrne","year":"2016","journal-title":"Cell Systems"},{"issue":"6","key":"pcbi.1008231.ref006","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1016\/j.bpj.2014.01.026","article-title":"In Vitro Reconstitution of a CaMKII Memory Switch by an NMDA Receptor-Derived Peptide","volume":"106","author":"H Urakubo","year":"2014","journal-title":"Biophysical Journal"},{"key":"pcbi.1008231.ref007","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.10644","article-title":"Bistability of a coupled Aurora B kinase-phosphatase system in cell division","volume":"5","author":"AV Zaytsev","year":"2016","journal-title":"eLife"},{"issue":"17","key":"pcbi.1008231.ref008","doi-asserted-by":"crossref","first-page":"R812","DOI":"10.1016\/j.cub.2013.06.047","article-title":"Building Synthetic Memory","volume":"23","author":"MC Inniss","year":"2013","journal-title":"Current Biology"},{"issue":"11","key":"pcbi.1008231.ref009","doi-asserted-by":"crossref","first-page":"R458","DOI":"10.1016\/j.cub.2012.03.045","article-title":"Bistability, Bifurcations, and Waddington\u2019s Epigenetic Landscape","volume":"22","author":"JE Ferrell","year":"2012","journal-title":"Current Biology"},{"issue":"4","key":"pcbi.1008231.ref010","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.copbio.2008.06.009","article-title":"Uncovering mechanisms of bistability in biological systems","volume":"19","author":"JR Pomerening","year":"2008","journal-title":"Current Opinion in Biotechnology"},{"issue":"12","key":"pcbi.1008231.ref011","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.tibs.2014.10.002","article-title":"Ultrasensitivity part III: cascades, bistable switches, and oscillators","volume":"39","author":"JE Ferrell","year":"2014","journal-title":"Trends in Biochemical Sciences"},{"issue":"1","key":"pcbi.1008231.ref012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0009-2509(88)87122-7","article-title":"Chemical Reaction Network Structure and the Stability of Complex Isothermal Reactors\u2014II. 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