Evidence map›Paper›PMID 27189187›Full record

ArticleNature communications2016

Structure of human Cdc45 and implications for CMG helicase function.

Aline C Simon, Vincenzo Sannino, Vincenzo Costanzo, Luca Pellegrini

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
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

57 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Structure of the Saccharolobus solfataricus GINS tetramer.Acta crystallographica. Section F, Structural biology communications · 2025
    Article
  7. Article
  8. Transcriptional and functional regulation of cell cycle and UV response by PPARβ in human skin epidermal cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  9. Article
  10. Article
  11. A second hotspot for pathogenic exon-skipping variants in CDC45.European journal of human genetics : EJHG · 2024
    Article
  12. Induction of the humanMolecular medicine reports · 2024
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. BiallelicJournal of medical genetics · 2022
    Article
  19. Article
  20. The intra-S phase checkpoint directly regulates replication elongation to preserve the integrity of stalled replisomes.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
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

4 authors at 2 institutions in 2 countries.

Aline C SimonDepartment of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
Vincenzo SanninoDNA Metabolism Laboratory, FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy.
Vincenzo CostanzoDNA Metabolism Laboratory, FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy.
Luca PellegriniDepartment of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.ORCID 0000-0002-9300-497X
IFOM · ITUniversity of Cambridge · GB

Funding

European Research Council 614541Wellcome Trust
6 · The paper itself

Abstract

Cell division cycle protein 45 (Cdc45) is required for DNA synthesis during genome duplication, as a component of the Cdc45-MCM-GINS (CMG) helicase. Despite its essential biological function, its biochemical role in DNA replication has remained elusive. Here we report the 2.1-Å crystal structure of human Cdc45, which confirms its evolutionary link with the bacterial RecJ nuclease and reveals several unexpected features that underpin its function in eukaryotic DNA replication. These include a long-range interaction between N- and C-terminal DHH domains, blocking access to the DNA-binding groove of its RecJ-like fold, and a helical insertion in its N-terminal DHH domain, which appears poised for replisome interactions. In combination with available electron microscopy data, we validate by mutational analysis the mechanism of Cdc45 association with the MCM ring and GINS co-activator, critical for CMG assembly. These findings provide an indispensable molecular basis to rationalize the essential role of Cdc45 in genomic duplication.

Indexed as

DNA ReplicationAmino Acid SequenceAnimalsBacterial ProteinsCell Cycle ProteinsChromosomal Proteins, Non-HistoneCrystallography, X-RayDNA HelicasesExodeoxyribonucleasesFemaleHumansMinichromosome Maintenance ProteinsProtein ConformationXenopus laevisBacterial ProteinsCDC45 protein, humanCell Cycle ProteinsChromosomal Proteins, Non-HistoneDNA HelicasesExodeoxyribonucleasesMinichromosome Maintenance ProteinsrecJ protein, Bacteria

Identifiers

PMID27189187
PMCPMC4873980
OpenAlexW2406084358

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.