ArticleCellular and molecular life sciences : CMLS2020
Characterization of the dimeric CMG/pre-initiation complex and its transition into DNA replication forks.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in patients with primary non-M3 AML is associated with a worse prognosis.Blood research · 2024Article
- S-CDK-regulated bipartite interaction of Mcm10 with MCM is essential for DNA replication.Frontiers in cell and developmental biology · 2024Article
- Review
- CDC45 modulates MCM7 expression and inhibits cell proliferation by suppressing the PI3K/AKT pathway in acute myeloid leukemia.American journal of translational research · 2021Article
- Caught in the act: structural dynamics of replication origin activation and fork progression.Biochemical Society transactions · 2020Review
- The acetyltransferase Eco1 elicits cohesin dimerization during S phase.The Journal of biological chemistry · 2020Article
- Review
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Authors and funding
9 authors.
Funding
Abstract
The pre-initiation complex (pre-IC) has been proposed for two decades as an intermediate right before the maturation of the eukaryotic DNA replication fork. However, its existence and biochemical nature remain enigmatic. Here, through combining several enrichment strategies, we are able to isolate an endogenous dimeric CMG-containing complex (designated as d-CMG) distinct from traditional single CMG (s-CMG) and in vitro reconstituted dimeric CMG. D-CMG is assembled upon entry into the S phase and shortly matures into s-CMG/replisome, leading to the fact that only ~ 5% of the total CMG-containing complexes can be detected as d-CMG in vivo. Mass spectra reveal that RPA and DNA Pol α/primase co-purify with s-CMG, but not with d-CMG. Consistently, the former fraction is able to catalyze DNA unwinding and de novo synthesis, while the latter catalyzes neither. The two CMGs in d-CMG display flexibly orientated conformations under an electronic microscope. When DNA Pol α-primase is inactivated, d-CMG % rose up to 29%, indicating an incomplete pre-IC/fork transition. These findings reveal biochemical properties of the d-CMG/pre-IC and provide in vivo evidence to support the pre-IC/fork transition as a bona fide step in replication initiation.
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Registered trials
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