ArticleProceedings of the National Academy of Sciences of the United States of America2014
CMG helicase and DNA polymerase ε form a functional 15-subunit holoenzyme for eukaryotic leading-strand DNA replication.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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118 citing papers in PubMed, 175 citations in OpenAlex.
- Response of the replisome to araA and araC suggests a mechanism for arabinosyl nucleoside tolerance.The EMBO journal · 2026Article
- Reconstituting human and SV40 replisomes with Okazaki fragment maturation reveals synchronized leading- and lagging-strand synthesis.Nature communications · 2026Article
- ATP is dispensable for E. coli DNA replication and eukaryotic helicase activity.Nature communications · 2026Article
- DNA Polymerase α has pyrimidine dimer translesion activity that is suppressed during normal replication.bioRxiv : the preprint server for biology · 2026Article
- Article
- Asymmetrical recognition and processing of double-strand breaks formed during DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Evidence for a functional interaction between yeast Pol ε and PCNA in vivo.Nucleic acids research · 2025Article
- Structure of the human CTF18-RFC clamp loader bound to PCNA.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms and genomic implications of break-induced replication.Nature structural & molecular biology · 2025Review
- Leading and lagging strand abasic sites differentially affect vertebrate replisome progression but involve analogous bypass mechanisms.Nucleic acids research · 2025Article
- DNA polymerase α-primase can function as a translesion DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The proofreading mechanism of the human leading-strand DNA polymerase ε holoenzyme.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comprehensive whole-genome sequencing reveals origins of mutational signatures associated with aging, mismatch repair deficiency and temozolomide chemotherapy.Nucleic acids research · 2025Article
- Site directed mutagenesis reveals functional importance of conserved amino acid residues within the N-terminal domain of Dpb2 in budding yeast.Archives of microbiology · 2024Article
- Revised mechanism of hydroxyurea-induced cell cycle arrest and an improved alternative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A common mechanism for recruiting the Rrm3 and RTEL1 accessory helicases to the eukaryotic replisome.The EMBO journal · 2024Article
- Single-molecule characterization of SV40 replisome and novel factors: human FPC and Mcm10.Nucleic acids research · 2024Article
- Mechanism of PCNA loading by Ctf18-RFC for leading-strand DNA synthesis.Science (New York, N.Y.) · 2024Article
- A Biophysics Toolbox for Reliable Data Acquisition and Processing in Integrated Force-Confocal Fluorescence Microscopy.ACS photonics · 2024Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
DNA replication in eukaryotes is asymmetric, with separate DNA polymerases (Pol) dedicated to bulk synthesis of the leading and lagging strands. Pol α/primase initiates primers on both strands that are extended by Pol ε on the leading strand and by Pol δ on the lagging strand. The CMG (Cdc45-MCM-GINS) helicase surrounds the leading strand and is proposed to recruit Pol ε for leading-strand synthesis, but to date a direct interaction between CMG and Pol ε has not been demonstrated. While purifying CMG helicase overexpressed in yeast, we detected a functional complex between CMG and native Pol ε. Using pure CMG and Pol ε, we reconstituted a stable 15-subunit CMG-Pol ε complex and showed that it is a functional polymerase-helicase on a model replication fork in vitro. On its own, the Pol2 catalytic subunit of Pol ε is inefficient in CMG-dependent replication, but addition of the Dpb2 protein subunit of Pol ε, known to bind the Psf1 protein subunit of CMG, allows stable synthesis with CMG. Dpb2 does not affect Pol δ function with CMG, and thus we propose that the connection between Dpb2 and CMG helps to stabilize Pol ε on the leading strand as part of a 15-subunit leading-strand holoenzyme we refer to as CMGE. Direct binding between Pol ε and CMG provides an explanation for specific targeting of Pol ε to the leading strand and provides clear mechanistic evidence for how strand asymmetry is maintained in eukaryotes.
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