The role of DDK and Treslin-MTBP in coordinating replication licensing and pre-initiation complex formation

Volpi, Ilaria, Gillespie, Peter J., Chadha, Gaganmeet Singh and Blow, Julian (2021) The role of DDK and Treslin-MTBP in coordinating replication licensing and pre-initiation complex formation. Open Biology, 11 (10). ISSN 2046-2441

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Treslin/Ticrr is required for the initiation of DNA replication and binds to MTBP (Mdm2 Binding Protein). Here we show that in Xenopus egg extract, MTBP forms an elongated tetramer with Treslin containing two molecules of each protein. Immunodepletion and add-back experiments show that Treslin-MTBP is rate-limiting for replication initiation. It is recruited onto chromatin before S phase starts and recruitment continues during S phase. We show that DDK activity both increases and strengthens the interaction of Treslin-MTBP with licensed chromatin. We also show that DDK activity cooperates with CDK activity to drive the interaction of Treslin-MTBP with TopBP1 which is a regulated crucial step in pre-Initiation Complex formation. These results suggest how DDK works together with CDKs to regulate Treslin-MTBP and plays a crucial in selecting which origins will undergo initiation.

Item Type: Article
Additional Information: Funding information: This work was supported by CR-UK programme grant C303/A14301 and Wellcome Trust Investigator award WT096598MA. I.V. was supported by a BBSRC studentship. We would like to acknowledge help from Dr. Sara ten Have and Kelly Hodge of the GRE Proteomics Support Team at the University of Dundee (Wellcome Trust Strategic Award 097945/Z/11/Z).
Uncontrolled Keywords: dna replication,mtbp,sld7,treslin,ticrr,sld3,topbp1,dbp11,xenopus,cdk,cdc7,ddk,pp1,simurosertib,cell cycle,biochemistry, genetics and molecular biology(all),neuroscience(all),immunology ,/dk/atira/pure/subjectarea/asjc/1300
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Depositing User: LivePure Connector
Date Deposited: 10 Jun 2024 09:30
Last Modified: 17 Jun 2024 08:30
DOI: 10.1098/rsob.210121

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