Download The protein that assesses distances

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
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