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ID:40364742
大小:674.42 KB
页数:12页
时间:2019-08-01
《Telomeres Protecting chromosomes against genome instability》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、focusonGenomeinstabilityREVIEWSTelomeres:protectingchromosomesagainstgenomeinstabilityRoderickJ.O’SullivanandJanKarlsederAbstract
2、Thenaturalendsoflinearchromosomesrequireuniquegeneticandstructuraladaptationstofacilitatetheprotectionofgeneticmaterial.Thi
3、sisachievedbythesequestrationofthetelomericsequenceintoaprotectivenucleoproteincapthatmaskstheendsfromconstitutiveexposuretotheDNAdamageresponsemachinery.Whentelomeresareunmasked,genomeinstabilityarises.Balancingcappingrequirementswithtelomerereplicatio
4、nandtheenzymaticprocessingstepsthatareobligatoryfortelomerefunctionisacomplexproblem.TelomericproteinsandtheirinteractingfactorscreateanenvironmentatchromosomeendsthatinhibitsDNArepair;however,therepairmachineryisessentialforpropertelomerefunction.Linea
5、rDNAfragmentsaretoxictomammaliancellsanditssubstrate(BOX1).ItisnotclearhowtheGoverhangG-quadruplexAhigher‑orderDNAstructureeffectivemechanismshaveevolvedtodealwiththem.providesprotectionfromthepathwaysthatdetectandconsistingofGquartetsinThesemechanismsi
6、nvolvesignallingcascades,resultingprocessbrokenDNA,butithasbeenproposedthatitwhichguanosineresiduesareinthedetection,enzymaticdegradationorrepairofthecanbesequesteredintoalassolikestructureknownasdonorsandacceptorsinafragments,cellcyclearrestand/orcelld
7、eath.FailuretotheTloop3(FIG.1).TheclosedconfigurationoftheTloopG–Gbasepair.ThisstructureisanobstacletothemovingappropriatelyrespondtobrokenDNAcanresultintheprovidesaprotectivecapthatdefinesthenaturalendofreplicationfork.unequaldistributionofgeneticmater
8、ialduringcelldivithechromosomeandmasksthetelomerefromtheDNAsion,genomeinstabilityand,eventually,thedevelopmentdamageresponse(DDR)machinery(FIG.2).Therefore,Fragilesiteofmalignancies.thegenerationandmanipulationoftheGoverhangbyAsiteinachromosomeatThenatu
9、ralendsoflinearchromosomesresembletelomeraseintelomerasepositivecellsisanimportantwhichbreaksfrequentlyoccur.DNAbreaksbutdifferinthattheirrepairwouldleadtopointofconvergenceofendprotectionandtelomeredeleteriouschromosomefusionsan
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