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- W4384559094 abstract "CMG (Cdc45-MCM-GINS) helicase assembly at the replication origin is the culmination of eukaryotic DNA replication initiation. This process can be reconstructed in vitro using defined factors in Saccharomyces cerevisiae; however, in vertebrates, origin-dependent CMG formation has not yet been achieved partly due to the lack of a complete set of known initiator proteins. Since a microcephaly gene product, DONSON, was reported to remodel the CMG helicase under replication stress, we analyzed its role in DNA replication using a Xenopus cell-free system. We found that DONSON was essential for the replisome assembly. In vertebrates, DONSON physically interacted with GINS and Polε via its conserved N-terminal PGY and NPF motifs, and the DONSON-GINS interaction contributed to the replisome assembly. DONSON's chromatin association during replication initiation required the pre-replicative complex, TopBP1, and kinase activities of S-CDK and DDK. Both S-CDK and DDK required DONSON to trigger replication initiation. Moreover, human DONSON could substitute for the Xenopus protein in a cell-free system. These findings indicate that vertebrate DONSON is a novel initiator protein essential for CMG helicase assembly." @default.
- W4384559094 created "2023-07-18" @default.
- W4384559094 creator A5006752812 @default.
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- W4384559094 date "2023-07-17" @default.
- W4384559094 modified "2023-10-09" @default.
- W4384559094 title "Novel role of DONSON in CMG helicase assembly during vertebrate DNA replication initiation" @default.
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- W4384559094 doi "https://doi.org/10.15252/embj.2023114131" @default.
- W4384559094 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37458194" @default.
- W4384559094 hasPublicationYear "2023" @default.
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