Telomeres Protecting chromosomes against genome instability

《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