Cell Size Checkpoint Control by the Retinoblastoma Tumor Suppressor Pathway 英文参考文献.docVIP

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Cell Size Checkpoint Control by the Retinoblastoma Tumor Suppressor Pathway 英文参考文献.doc

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Cell Size Checkpoint Control by the Retinoblastoma Tumor Suppressor Pathway 英文参考文献

CellSizeCheckpointControlbythe RetinoblastomaTumorSuppressorPathway Su-Chiung Fang, Chris de losReyes, James G.Umen* PlantBiologyLaboratory,TheSalkInstitute,LaJolla,California,UnitedStatesofAmerica Sizecontrolisessentialforallproliferatingcells,andisthoughttoberegulatedbycheckpointsthatcouplecellsizeto cell cycle progression. The aberrant cell-size phenotypes caused by mutations in the retinoblastoma (RB) tumor suppressorpathwayareconsistentwitharoleinsizecheckpointcontrol,butindirecteffectsonsizecausedbyaltered cell cycle kinetics are difficult to rule out. The multiple fission cell cycle of the unicellular alga Chlamydomonas reinhardtiiuncouplesgrowthfromdivision,allowingdirectassessmentoftherelationshipbetweensizephenotypes and checkpoint function. Mutations in the C. reinhardtii RB homolog encoded by MAT3 cause supernumerous cell divisionsandsmallcells,suggestingaroleforMAT3insizecontrol.Weidentifiedsuppressorsofanmat3nullallele that had recessive mutations in DP1 or dominant mutations in E2F1, loci encoding homologs of a heterodimeric transcription factor that is targeted by RB-related proteins. Significantly, we determined that the dp1 and e2f1 phenotypeswerecausedbydefectsinsizecheckpointcontrolandwerenotduetoalengthenedcellcycle.Despite theircelldivisiondefects,mat3,dp1,ande2f1mutantsshowedalmostnochangesinperiodictranscriptionofgenes inducedduringSphaseandmitosis,manyofwhichareconservedtargetsoftheRBpathway.Conversely,wefound thatregulationofcellsizewasunaffectedwhenSphaseandmitotictranscriptionwereinhibited.Ourdataprovide directevidencethattheRBpathwaymediatescellsizecheckpointcontrolandsuggestthatsuchcontrolisnotdirectly coupledtothemagnitudeofperiodiccellcycletranscription. Citation:FangSC,delosReyesC,UmenJG(2006)Cellsizecheckpointcontrolbytheretinoblastomatumorsuppressorpathway.PLoSGenet2(10):e167. DOI:10.1371/ journal.pgen.0020167 proteins has been shown to affect cell size and cell cycle controlinanimalsandplantsinamannerthatisconsist