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Theproteinthatassessesdistances TomoveDNA“beads”alongthestrand,themoleculeknowshowlongitis May20,2016 AproteinoftheISWIfamily(ImitationSwitch,ornucleosomeremodellingmotors)isendowed withaspecialproperty:despitehavingnoorganofsenseitisnonethelessabletoassessthe lengthofDNAstrands.AstudyjustpublishedintheJournalofStatisticalMechanics:Theoryand ExperimentandcarriedoutbySISSA,theMAXPlanckInstituteandtheNIHhasdiscoveredhowit works. Pictureachromosomeasastringofbeads.Thebeadsareinfactcallednucleosomesandare formedbytheDNAstrandthatmakesupthechromosomeitself,tightlywrappedaround proteins,calledhistones,whichactabitlikespools.Nucleosomesarejoinedtooneotherbya segment,ofvaryinglength,ofthesamestrandofDNA.The“beads”canbemovedalongthe strand,groupedclosetogetherormovedapart,bytheactionofspecialproteinscalled “remodellingmotors”.Onetypeofthesemotorsarrangesthenucleosomesequidistantlyonthe “stringofbeads”.Toknowwheretomovethenucleosomes,themotorsneedtoassessthelength ofthesegmentsjoiningthem.Andthisiswherethequestionarises:howcanasinglemolecule “sense”howlongapieceofDNAis? AnaMariaFlorescu,researchscientistattheInternationalSchoolforAdvancedStudies(SISSA)in Trieste,andKuniIwasa,fromtheUSNationalInstitutesofHealth(NIH),haveansweredthis questionbymeansofatheoreticalstudy.BothFlorescuandIwasawereattheMaxPlanck InstituteforPhysicsofComplexSystemsinDresdenwhentheystartedtheirworkforthis research.“Itisindeeda‘sensory’issue,butlet’snotforgetwearedealingwithproteincomplexes, whichdon’thaveorgansofsense”,explainsFlorescu. FlorescuandIwasawereinspiredbypreviousexperimentalresults,andtheyconstructedamodel ofthesystem(nucleosomes,strandsandremodellingmotors,immersedinafluidenvironment). “WhatweobservedinourcalculationsisthatthelongertheDNAsegmentbetweenone nucleosomeandthenexttheshorterthetimeittakesthemotortobindtoit”.Infactthestrands immersedinfluidtendtofluctuaterandomlyandthemagnitudeandspeedoftheirmovement dependonthelengthofthesegment.Inpractice,theshorterthesegment,thefasteritoscillates: “inthiscase,themoleculehasmoretroublecapturingthesegment,anditcannotcarryoutits actionuntilitbindstoit”.Thetimeittakesthemotortobindtothesegmentisthereforean indicatorofthelengthofthesegmentitself. UnpackingthestrandtoallowDNAtowork TheultimatefunctionofDNAisproteinsynthesis,aprocessthatstartswiththefirstcrucialstep ofgenetranscription:piecesofcodecontainedinthegenesarecopiedtobeusedasamatrixto buildnewproteins.Forthistohappen,thenitrogenbasesthatmakeuptheDNAstrandneedto beaccessible.Whentheyaretightlypackedaroundthehistones,theyareunusable.Their rearrangementbytheremodellingmotorsiscrucialforfreeingthem. “DNAistightlypackagedbecauseotherwiseitwouldn’tfitinsidethecellnucleus,aswe’retalking aboutovertwometresofstrandintotalifweconsiderthecompletehumangenome.This, though,hasthedisadvantageofhavingtounpackiteachtimeit’sneeded,ataskcarriedoutby theremodellingmotorsthatmakethechromatinstrandaccessiblesothatthetranscription processcantakeplace”explainsFlorescu. Soitiseasytounderstandhowimportanttheseremodellingmoleculesareforthebody’shealth: abreakdownofthemechanismblockstranscriptionandthusproteinsynthesis.And,indeed, “somestudieshavelinkedcertaintypesofcancerwiththeabsenceorlimitedpresenceof remodellingmotors”,concludesFlorescu. USEFULLINKS: • OriginalPaperontheJournalofStatisticalMechanics:TheoryandExperiment http://dx.doi.org/10.1088/1742-5468/2016/05/054030 IMAGES: • DNA–Credits:AnaMariaFlorescu Contact: Pressoffice: [email protected] Tel:(+39)0403787644|(+39)366-3677586 viaBonomea,265 34136Trieste MoreinformationaboutSISSA:www.sissa.it