ArticleJournal of molecular biology2022
The Rate-limiting Step of DNA Synthesis by DNA Polymerase Occurs in the Fingers-closed Conformation.
Article in Journal of molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Structures of human telomerase with BIBR1532 reveal novel mechanism of inhibition.Nature chemical biology · 2026Article
- Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε.Nature structural & molecular biology · 2024Article
- Strategies and procedures to generate chimeric DNA polymerases for improved applications.Applied microbiology and biotechnology · 2024Review
- Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90.Nature communications · 2024Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
DNA polymerases maintain genomic integrity by copying DNA with high fidelity, part of which relies on the polymerase fingers opening-closing transition, a series of conformational changes during the DNA synthesis reaction cycle. Fingers opening and closing has been challenging to study, mainly due to the need to synchronise molecular ensembles. We previously studied fingers opening-closing on single polymerase-DNA complexes using single-molecule FRET; however, our work was limited to pre-chemistry reaction steps. Here, we advance our analysis to extensible substrates, and observe DNA polymerase (Pol) conformational changes across the entire DNA polymerisation reaction in real-time, gaining direct access to an elusive post-chemistry step rate-limiting for DNA synthesis. Our results showed that Pol adopts the fingers-closed conformation during polymerisation, and that the post-chemistry rate-limiting step occurs in the fingers-closed conformation. We found that fingers-opening in the Pol-DNA binary complex in the absence of polymerisation is slow (∼5.3 s
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