Editing Hysteresis (section)

==== Biochemical systems: regulating the cell cycle in ''xenopus laevis'' egg extracts ====
Cells advancing through the cell cycle must make an irreversible commitment to mitosis, ensuring they do not revert to interphase before successfully segregating their chromosomes. A mathematical model of cell-cycle progression in cell-free egg extracts from frogs suggests that hysteresis in the molecular control system drives these irreversible transitions into and out of mitosis.<ref>{{Cite journal |last1=Chow |first1=Y. W. |last2=Pietranico |first2=R. |last3=Mukerji |first3=A. |date=1975-10-27 |title=Studies of oxygen binding energy to hemoglobin molecule |url=https://pubmed.ncbi.nlm.nih.gov/6 |journal=Biochemical and Biophysical Research Communications |volume=66 |issue=4 |pages=1424–1431 |doi=10.1016/0006-291x(75)90518-5 |issn=0006-291X |pmid=6}}</ref> Here, Cdc2 (Cyclin-dependent kinase 1 or CDK1) is responsible for mitotic entry and exit such that binding of cyclin B forms a complex called Maturation-Promoting Factor (MPF).<ref>{{Cite journal |last1=Hoffmann |first1=I. |last2=Clarke |first2=P. R. |last3=Marcote |first3=M. J. |last4=Karsenti |first4=E. |last5=Draetta |first5=G. |date=January 1993 |title=Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis |journal=The EMBO Journal |volume=12 |issue=1 |pages=53–63 |doi=10.1002/j.1460-2075.1993.tb05631.x |issn=0261-4189 |pmid=8428594|pmc=413175 }}</ref> The activation threshold for mitotic entry was found to be between 32 and 40 nM cyclin B in the frog extracts while the inactivation threshold for exiting mitosis was lower, between 16 and 24 nM cyclin B. The higher threshold for mitotic entry compared to the lower threshold for mitotic exit indicates hysteresis, a hallmark of history-dependent behavior in the system. Concentrations between 24 and 32 nM cyclin B demonstrated bistability, where the system could exist in either interphase or mitosis, depending on its prior state (history). Though, the cell cycle is not completely irreversible, the difference in thresholds is enough for growth and survival of the cells.

Hysteric thresholds in biological systems are not definite and can be recalibrated. For example, unreplicated DNA or chromosomes inhibits Cdc25 phosphatase and maintains Wee1 kinase activity.<ref>{{Cite journal |last1=Perry |first1=Jennifer A. |last2=Kornbluth |first2=Sally |date=2007-05-04 |title=Cdc25 and Wee1: analogous opposites? |journal=Cell Division |language=en |volume=2 |pages=12 |doi=10.1186/1747-1028-2-12 |doi-access=free |pmc=1868713 |pmid=17480229}}</ref> This prevents the activation of Cyclin B-Cdc2, effectively raising the threshold for mitotic entry. As a result, the cell delays the transition to mitosis until replication is complete, ensuring genomic integrity. Other instances may be DNA damage and unattached chromosomes during the spindle assembly checkpoint.<ref>{{Cite journal |last1=Marniemi |first1=J. |last2=Parkki |first2=M. G. |date=1975-09-01 |title=Radiochemical assay of glutathione S-epoxide transferase and its enhancement by phenobarbital in rat liver in vivo |url=https://pubmed.ncbi.nlm.nih.gov/9 |journal=Biochemical Pharmacology |volume=24 |issue=17 |pages=1569–1572 |doi=10.1016/0006-2952(75)90080-5 |issn=0006-2952 |pmid=9}}</ref>