Connecting chromosomes, crisis, and cancer.Science

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1、GENOMEINSTABILITY61.P.V.Jallepallietal.,Cell105,445(2001).67.S.Gruber,K.Nasmyth,unpublisheddata.74.S.Kaitna,P.Pasierbek,M.Jantsch,J.Loidl,M.62.J.Mei,X.Huang,P.Zhang,Curr.Biol.11,119768.I.Waizenegger,J.F.Gimenez-Abian,D.Wernic,J.M.Glotzer,Curr.Biol.12,798(2002).

2、(2001).Peters,personalcommunication.75.M.Peteretal.,NatureCellBiol.3,83(2001).63.Z.Wang,R.Yu,S.Melmed,Mol.Endocrinol.15,187069.C.F.Lehner,personalcommunication.76.F.E.Taieb,S.D.Gross,A.L.Lewellyn,J.L.Maller,(2001).70.N.C.D.Hornig,P.P.Knowles,N.Q.McDonald,F.Curr

3、.Biol.11,508(2001).64.O.Stemmann,H.Zou,S.A.Gerber,S.P.Gygi,M.W.Uhlmann,Curr.Biol.inpress.Kirschner,Cell107,715(2001).71.S.B.Buonomoetal.,Cell103,387(2000).77.F.A.Janssens,LaCellule25,387(1909).65.S.L.Holloway,M.Glotzer,R.W.King,A.W.Murray,72.M.F.Siomosetal.,Cur

4、r.Biol.11,1825(2001).78.IthankS.HaufforsupplyingFig.1,H.TkadletzforCell73,1393(1993).73.E.Rogers,J.D.Bishop,J.A.Waddle,J.M.Schuma-drawingthefigures,andJ.M.Petersforcommentson66.L.Aravind,E.V.Koonin,Proteins46,355(2002).cher,R.Lin,J.CellBiol.157,219(2002).themanu

5、script.REVIEWConnectingChromosomes,Crisis,andCancerRichardS.MaserandRonaldA.DePinho*Cancerisadiseaseofimpairedgenomestability.ThemolecularforcesthatvationofcellularcheckpointsnotunlikemaintaingenomeintegrityandsensealteredchromosomestructurearethoseprovokedbyDN

6、Adamage[reviewedinvariablysubvertedincancercells.Here,weexplorethecontrastingin(13–15)].Inhumancellcultures,shortcontributionsoftelomeresintheinitiationandsuppressionofcancerandtelomeresresultinactivationoftheHayflickreviewtheevidencesupportingarolefortelomered

7、ysfunctionasalimit(MortalityStage1orsenescence),andmechanismdrivingtheradicalchromosomalaberrationsthattypifycancerthecellsstopdividing[reviewedin(16)].genomes.RecentworksuggeststhatpassageofcellsthroughcrisisintheHowever,theHayflicklimitcanbereadilysettingofde

8、activatedDNAdamagecheckpointsprovidesamutationalbreachedbyinactivationofthep53andRbmechanismthatcangeneratethediversegeneticalterationsrequiredforgrowthinhibitorypathways.Co