Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity 英文参考文献.docVIP
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Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity 英文参考文献
DynamicsofRad9ChromatinBindingandCheckpoint
FunctionAreMediatedbyItsDimerizationandAreCell
Cycle–RegulatedbyCDK1Activity
MagdaGranata1.,FedericoLazzaro1.,DanieleNovarina1,DavidePanigada1,FabioPuddu1 ,Carla
ManuelaAbreu2,RameshKumar2,MurielGrenon2,NoelF.Lowndes2,PaoloPlevani1* ,Marco
Muzi-Falconi1*
1Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita` degli Studi di Milano, Milano, Italy, 2Centre for Chromosome Biology, School of Natural Science,
NationalUniversityofIrelandGalway,Galway,Ireland
Abstract
Saccharomycescerevisiae Rad9isrequiredforaneffectiveDNAdamageresponsethroughoutthecellcycle.Assembly of
Rad9onchromatinafterDNAdamageispromotedbyhistonemodificationsthatcreatedockingsitesforRad9recruitment,
allowing checkpoint activation. Rad53 phosphorylation is also dependent upon BRCT-directed Rad9 oligomerization;
however,thecrosstalkbetweenthesemoleculardeterminantsandtheirfunctionalsignificancearepoorlyunderstood.Here
wereportthat,intheG1andMphasesofthecellcycle,bothconstitutiveandDNAdamage-dependentRad9chromatin
associationrequireitsBRCTdomains.InG1cells,GSTorFKBPdimerizationmotifscansubstitutetotheBRCTdomainsfor
Rad9 chromatin binding and checkpoint function. Conversely, forced Rad9 dimerization in M phase fails to promote its
recruitmentontoDNA,althoughitsupportsRad9checkpointfunction.Infact,aparallelpathway,independentonhistone
modifications and governed by CDK1 activity, allows checkpoint activation in the absence of Rad9 chromatin binding.
CDK1-dependentphosphorylationofRad9onSer11leadstospecificinteractionwithDpb11,allowingRad53activationand
bypassingtherequirementforthehistonebranch.
Citation:GranataM,LazzaroF,NovarinaD,PanigadaD,PudduF,etal.(2010)DynamicsofRad9ChromatinBindingandCheckpointFunctionAreMediatedbyIts
DimerizationandAreCellCycle–RegulatedbyCDK1Activity.PLoSGenet6(8):e1001047.doi:10.1371/journal.pgen.1001047
Editor:GregoryP.Copenhaver,TheUniversityofNorthCarolinaatChapelHill,UnitedStatesofAmerica
ReceivedDecember24,2009
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