REPORT◥CELLDIVISIONASUMO-ubiquitinrelayrecruitsproteasomestochromosomeaxestoregulatemeioticrecombinationH.B.D.PrasadaRao,1,2HuanyuQiao,1,2ShubhangK.Bhatt,2LoganR.J.Bailey,2HungD.Tran,2SarahL.Bourne,2WendyQiu,2AnushaDeshpande,2AjayN.Sharma,2ConnorJ.Beebout,2RobertoJ.Pezza,3NeilHunter1,2,4,5*Meiosisproduceshaploidgametesthroughasuccessionofchromosomalevents,includingpairing,synapsis,andrecombination.Mechanismsthatorchestratetheseeventsremainpoorlyunderstood.WefoundthattheSUMO(smallubiquitin-likemodifier)–modificationandubiquitin-proteasomesystemsregulatethemajoreventsofmeioticprophaseinmouse.InterdependentlocalizationofSUMO,ubiquitin,andproteasomesalongchromosomeaxeswasmediatedlargelybyRNF212andHEI10,twoE3ligasesthatarealsoessentialforcrossoverrecombination.RNF212-dependentSUMOconjugationeffectedacheckpointlikeprocessthatstallsrecombinationbyrenderingtheturnoverofasubsetofrecombinationfactorsdependentonHEI10-mediatedubiquitylation.WeproposethatSUMOconjugationestablishesapreconditionfordesignatingcrossoversitesviaselectiveproteinstabilization.Thus,meioticchromosomeaxesarehubsforregulatedproteolysisviaSUMO-dependentcontroloftheubiquitin-proteasomesystem.Meiosishalvesthechromosomecomple-mentviatwosuccessiveroundsofcelldivision.Accuratesegregationofhomol-ogouschromosomes(homologs)duringthefirstmeioticdivisionrequirestheirconnectionbychiasmata—theconjunctionofcrossingoverandsister-chromatidcohesion(1).Chiasmaformationistheculminationofanelaborateseriesofinterdependenteventsthatincludeprogrammedrecombinationandthepairingandsynapsisofhomologs.Eachhomol-ogcomprisestwosisterchromatids,whichareorganizedintoarraysofchromatinloopscon-nectedtoacommoncoreoraxis.Pairingandsynapsisarepromotedbyhomologousrecom-bination,whichoccursinphysicalandfunctionalassociationwiththeseaxes.Asmeiosisprogresses,axesalignandbecomeconnectedalongtheirlengthstoformsynaptonemalcomplexes(SCs).TheSUMO(smallubiquitin-likemodifier)–modification(SMS)andubiquitin-proteasome(UPS)systemsarekeyregulatorsof...
