Novel role of DONSON in CMG helicase assembly during vertebrate DNA replication initiation
By Yoshitami Hashimoto, Kota Sadano, Nene Miyata, Haruka Ito, Hirofumi Tanaka. 2023
37 citations recorded by the source corpus.
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.
Subfields: Cell Biology, Molecular Biology
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Citations in the corpus
- In silico protein interaction screening uncovers DONSON’s role in replication initiation (2023, background): “…with structure predictions in different organisms (table S1), evidence for DONSON-dependent GINS and CDC45 recruitment to chromatin in nuclear assembly egg extracts ( 42 , 43 ), and data from worms ( 44 ), our evidence suggests that DONSON is generally required for CMG assembly in metazoans.”
- DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in C. elegans (2023, unknown): “This suggests an evolutionarily conserved role for metazoan DONSON orthologues during DNA replication initiation, consistent with recent data for Xenopus DONSON (53, 54).”