Evidence map›Paper›PMID 33056978›Full record

ArticleNature communications2020

Evolution of DNA replication origin specification and gene silencing mechanisms.

Y Hu, A Tareen, Y-J Sheu, W T Ireland, C Speck, H Li, L Joshua-Tor, J B Kinney, B Stillman

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

30 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Article
  3. Genome sequence assembly and annotation ofNAR genomics and bioinformatics · 2025
    Article
  4. Article
  5. Article
  6. Compact Origins and Where to Find Them: ORC's Guide to Genome-Wide Licensing.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  7. Review
  8. DNA bending mediated by ORC is essential for replication licensing in budding yeast.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Gauge fixing for sequence-function relationships.PLoS computational biology · 2025
    Article
  14. Article
  15. Article
  16. Four decades of Eukaryotic DNA replication: From yeast genetics to high-resolution cryo-EM structures of the replisome.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  17. Gauge fixing for sequence-function relationships.bioRxiv : the preprint server for biology · 2024
    Article
  18. Article
  19. Review
  20. Mechanisms of chromatin-based epigenetic inheritance.Science China. Life sciences · 2022
    Review
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

9 authors at 5 institutions in 2 countries.

Y HuCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA.
A TareenCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA.
Y-J SheuCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA.
W T IrelandDepartment of Physics, California Institute of Technology, Pasadena, CA, 91125, USA.
C SpeckDNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, W12 0NN, London, UK.ORCID 0000-0001-6646-1692
H LiStructural Biology Program, Van Andel Institute, Grand Rapids, MI, 49503, USA.ORCID 0000-0001-8085-8928
L Joshua-TorCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA.ORCID 0000-0001-8185-8049
J B KinneyCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA.ORCID 0000-0003-1897-3778
B StillmanCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA. stillman@cshl.edu.ORCID 0000-0002-9453-4091
Cold Spring Harbor Laboratory · USCalifornia Institute of Technology · USHoward Hughes Medical Institute · USImperial College London · GBVan Andel Institute · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI David A Tuveson · 1987 to 2026
$118.9M
VIRAL TRANSACTIVATIONP01CA013106 · NCI · COLD SPRING HARBOR LABORATORY · PI William Richard McCombie · 1985 to 2026
$116.8M
REGULATION OF DNA REPLICATIONR01GM045436 · NIGMS · COLD SPRING HARBOR LABORATORY · PI STILLMAN, BRUCE W. · 1991 to 2025
$15.8M
Structural mechanism of DNA replicationR35GM131754 · NIGMS · VAN ANDEL RESEARCH INSTITUTE · PI Huilin Li · 2019 to 2026
$6.0M
Biophysical modeling of cis-regulatory complexes in transcription and splicing using massively parallel reporter assaysR35GM133777 · NIGMS · COLD SPRING HARBOR LABORATORY · PI KINNEY, JUSTIN B. · 2019 to 2023
$2.4M
Biotechnology and Biological Sciences Research Council BB/N000323/1Biotechnology and Biological Sciences Research Council BB/S001387/1Howard Hughes Medical InstituteNCI NIH HHS P01 CA013106NCI NIH HHS P30 CA045508NIGMS NIH HHS R01 GM045436NIGMS NIH HHS R35 GM131754NIGMS NIH HHS R35 GM133777Wellcome TrustWellcome Trust 107903/Z/15/Z
6 · The paper itself

Abstract

DNA replication in eukaryotic cells initiates from replication origins that bind the Origin Recognition Complex (ORC). Origin establishment requires well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. A 3.9 Å structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed that a loop within Orc2 inserts into a DNA minor groove and an α-helix within Orc4 inserts into a DNA major groove. Using a massively parallel origin selection assay coupled with a custom mutual-information-based modeling approach, and a separate analysis of whole-genome replication profiling, here we show that the Orc4 α-helix contributes to the DNA sequence-specificity of origins in S. cerevisiae and Orc4 α-helix mutations change genome-wide origin firing patterns. The DNA sequence specificity of replication origins, mediated by the Orc4 α-helix, has co-evolved with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA interference.

Indexed as

Gene Expression Regulation, FungalGene SilencingDNA, FungalDNA ReplicationEvolution, MolecularMutationOrigin Recognition ComplexProtein Conformation, alpha-HelicalReplication OriginSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeSubstrate SpecificityDNA, FungalORC2 protein, S cerevisiaeORC4 protein, S cerevisiaeOrigin Recognition ComplexSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeSIR4 protein, S cerevisiae

Identifiers

PMID33056978
PMCPMC7560902
OpenAlexW3093163345

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.