Evidence map›Paper›PMID 42733061›Full record

ArticleNature communications2026

Structural insights into Sld3-Sld7-dependent Cdc45 loading during replication initiation.

Yasunori Noguchi, Almutasem Saleh, Sarah Schneider, Marina E Ivanova, Zhuo Angel Chen, Lepakshi Ranjha, Ricardo Aramayo, Silvia Tognetti, Sarah V Faull, Juri Rappsilber and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yasunori Noguchi *DNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
Almutasem Saleh *DNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. a.saleh@lms.mrc.ac.uk.ORCID http://orcid.org/0000-0002-0156-4508
Sarah SchneiderDNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
Marina E IvanovaDNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
Zhuo Angel ChenTechnische Universität Berlin, Chair of Bioanalytics, Berlin, Germany.ORCID http://orcid.org/0000-0003-0811-8348
Lepakshi RanjhaDNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
Ricardo AramayoMRC Laboratory of Medical Sciences (LMS), London, United Kingdom.
Silvia TognettiDNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-7331-214X
Sarah V FaullDNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
Juri RappsilberTechnische Universität Berlin, Chair of Bioanalytics, Berlin, Germany.ORCID http://orcid.org/0000-0001-5999-1310
Christian SpeckDNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. chris.speck@imperial.ac.uk.ORCID http://orcid.org/0000-0001-6646-1692

Funding

Cancer Research UK (CRUK) DRCNPG-May21/100006EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 101119142RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/T005378/1RCUK | Medical Research Council (MRC) A652-5PY40Wellcome TrustWellcome Trust (Wellcome) 107903/Z/15/ZWellcome Trust (Wellcome) 227434
6 · The paper itself

Abstract

Regulated helicase activation by DDK kinase is central for genome stability. However, how DDK phosphorylation primes the MCM2-7 double hexamer (DH) for Sld3-Sld7 binding and Cdc45 loading remained unclear. We define this mechanism through cryo-EM structures of MCM2-7 DH-Sld3-Sld7 (MS) and MCM2-7 DH-Sld3-Sld7-Cdc45 (MSC). We reveal that the autoinhibitory Mcm4 tail engages not only Mcm4 but also Mcm6. Upon DDK-dependent phosphorylation, both of these sites become accessible. In the context of the MS structure, we identify that two short Sld3 motifs that contact Mcm4 and Mcm6 read out the DH phosphorylation state, while the Sld3 Treslin domain (STD) binds to Mcm2. In the MSC structure, Cdc45 dislodges the Sld3 STD from Mcm2, allowing Sld3 to position Cdc45 at the Mcm2/Mcm5 interface. Mutagenesis of the Sld3 STD-Cdc45 interface disrupts Cdc45 loading, validating this interaction. Together, our data reveal a phosphorylation-encoded mechanism coupling DDK-activated Mcm4/Mcm6 surfaces to distal Cdc45 placement, explaining how firing factors choreograph the DH-to-CMG transition.

Indexed as

Cell Cycle ProteinsDNA-Binding ProteinsDNA ReplicationNuclear ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCryoelectron MicroscopyMinichromosome Maintenance Complex Component 4Minichromosome Maintenance Complex Component 6Minichromosome Maintenance ProteinsPhosphorylationProtein BindingProtein DomainsProtein Serine-Threonine KinasesCDC45 protein, S cerevisiaeCDC7 protein, S cerevisiaeCell Cycle ProteinsDNA-Binding ProteinsMCM2 protein, S cerevisiaeMCM4 protein, S cerevisiaeMCM6 protein, S cerevisiaeMinichromosome Maintenance Complex Component 4Minichromosome Maintenance Complex Component 6Minichromosome Maintenance ProteinsNuclear ProteinsProtein Serine-Threonine KinasesSaccharomyces cerevisiae ProteinsSld3 protein, S cerevisiae

Identifiers

PMID42733061
PMCPMC13572456

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.