Evidence map›Paper›PMID 18772888›Full record

ArticleNature2008

The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix.

Hideharu Hashimoto, John R Horton, Xing Zhang, Magnolia Bostick, Steven E Jacobsen, Xiaodong Cheng

Open access · greenAbstract read
In one paragraph

Article in Nature, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers.

0numbers the graph read from it
0cells of the map it votes in
254citing papers in PubMed
11.4field-weighted citation impact, top 1% 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

254 citing papers in PubMed, 431 citations in OpenAlex.

  1. Article
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  8. A methylome-derived mbioRxiv : the preprint server for biology · 2026
    Article
  9. UHRF1 Controls the Timing of RAD51 Removal During DNA Damage Repair Through Suppressing RFWD3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  10. Review
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  12. Review
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194 more citing papers are in PubMed but not listed here.

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

6 authors at 3 institutions in 2 countries.

Hideharu HashimotoDepartment of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
John R Horton
Xing Zhang
Magnolia Bostick
Steven E Jacobsen
Xiaodong Cheng
Emory University · USHoward Hughes Medical Institute · USInstitute of Molecular and Cell Biology · RU

Funding

THREE-DIMENSIONAL STRUCTURE OF HHAI METHYLASER01GM049245 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHENG, XIAODONG · 1993 to 2017
$6.6M
Genetics of DNA methylation patterning of arabidopsis.R37GM060398 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JACOBSEN, STEVEN E · 2009 to 2018
$3.0M
Genetics of DNA Methylation Patterning of ArabidopsisR01GM060398 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JACOBSEN, STEVEN E · 2000 to 2008
$2.2M
Howard Hughes Medical InstituteNCI NIH HHS CA1263022NIGMS NIH HHS GM049245NIGMS NIH HHS GM060398NIGMS NIH HHS R01 GM049245NIGMS NIH HHS R01 GM060398NIGMS NIH HHS R37 GM060398
6 · The paper itself

Abstract

Maintenance methylation of hemimethylated CpG dinucleotides at DNA replication forks is the key to faithful mitotic inheritance of genomic methylation patterns. UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for maintenance methylation by interacting with DNA nucleotide methyltransferase 1 (DNMT1), the maintenance methyltransferase, and with hemimethylated CpG, the substrate for DNMT1 (refs 1 and 2). Here we present the crystal structure of the SET and RING-associated (SRA) domain of mouse UHRF1 in complex with DNA containing a hemimethylated CpG site. The DNA is contacted in both the major and minor grooves by two loops that penetrate into the middle of the DNA helix. The 5-methylcytosine has flipped completely out of the DNA helix and is positioned in a binding pocket with planar stacking contacts, Watson-Crick polar hydrogen bonds and van der Waals interactions specific for 5-methylcytosine. Hence, UHRF1 contains a previously unknown DNA-binding module and is the first example of a non-enzymatic, sequence-specific DNA-binding protein domain to use the base flipping mechanism to interact with DNA.

Indexed as

DNA Methylation5-MethylcytosineAnimalsBase SequenceCCAAT-Enhancer-Binding ProteinsCpG IslandsCrystallography, X-RayDNAHydrogen BondingHydrophobic and Hydrophilic InteractionsMiceModels, MolecularMolecular ConformationNuclear ProteinsProtein BindingProtein Structure, Tertiary5-MethylcytosineCCAAT-Enhancer-Binding ProteinsDNANuclear ProteinsUbiquitin-Protein LigasesUhrf1 protein, mouse

Identifiers

PMID18772888
PMCPMC2602803
OpenAlexW1977063334

What OpenQuestion holds

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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.