Cell Size at S Phase Initiation An Emergent Property of the G1S Network 英文参考文献.docVIP

CellSizeatSPhaseInitiation:AnEmergent PropertyoftheG1/SNetwork Matteo Barberis1,2[,Edda Klipp2[*,Marco Vanoni1,Lilia Alberghina1* 1DepartmentofBiotechnologyandBiosciences,UniversityofMilano-Bicocca,Milan,Italy,2Max-PlanckInstituteforMolecularGenetics,ComputationalSystemsBiology, Berlin,Germany Theeukaryoticcellcycleistherepeatedsequenceofeventsthatenablethedivisionofacellintotwodaughtercells.It is divided into four phases: G1, S, G2, and M. Passage through the cell cycle is strictly regulated by a molecular interaction network, which involves the periodic synthesis and destruction of cyclins that bind and activate cyclin- dependentkinasesthatarepresentinnonlimitingamounts.Cyclin-dependentkinaseinhibitorscontributetocellcycle control.Buddingyeastisanestablishedmodelorganismforcellcyclestudies,andseveralmathematicalmodelshave beenproposedforitscellcycle.AnareaofmajorrelevanceincellcyclecontrolistheG1toStransition.Inanygiven growth condition, it is characterized by the requirement of a specific, critical cell size, PS, to enter S phase. The molecularbasisofthiscontrolisstillunderdiscussion.TheauthorsreportamathematicalmodeloftheG1toSnetwork that newly takes into account nucleo/cytoplasmic localization, the role of the cyclin-dependent kinase Sic1 in facilitating nuclear import of its cognate Cdk1-Clb5, Whi5 control, and carbon source regulation of Sic1 and Sic1- containing complexes. The model was implemented by a set of ordinary differential equations that describe the temporal change of the concentration of the involved proteins and protein complexes. The model was tested by simulationinseveralgeneticandnutritionalsetupsandwasfoundtobeneatlyconsistentwithexperimentaldata.To estimatePS,theauthorsdevelopedahybridmodelincludingaprobabilisticcomponentforfiringofDNAreplication origins. Sensitivity analysis of PS provides a novel relevant conclusion: PS is an emergent property of the G1 to S networkthatstronglydependsongrowthrate. Citation:BarberisM,KlippE,VanoniM,Alber