Evidence map›Paper›PMID 35202575›Full record

ArticleMolecular cell2022

Structural insights into DNMT5-mediated ATP-dependent high-fidelity epigenome maintenance.

Juncheng Wang, Sandra Catania, Chongyuan Wang, M Jason de la Cruz, Beiduo Rao, Hiten D Madhani, Dinshaw J Patel

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Juncheng WangStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: wangj1@mskcc.org.
Sandra CataniaDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Chongyuan WangStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
M Jason de la CruzStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Beiduo RaoDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Hiten D MadhaniDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: hitenmadhani@gmail.com.
Dinshaw J PatelStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: pateld@mskcc.org.
Memorial Sloan Kettering Cancer Center · USUniversity of California, San Francisco · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Mechanisms of Gene SilencingR01GM071801 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Hiten D Madhani · 2005 to 2026
$7.1M
NCI NIH HHS P30 CA008748NIGMS NIH HHS R01 GM071801
6 · The paper itself

Abstract

Epigenetic evolution occurs over million-year timescales in Cryptococcus neoformans and is mediated by DNMT5, the first maintenance type cytosine methyltransferase identified in the fungal or protist kingdoms, the first dependent on adenosine triphosphate (ATP), and the most hemimethyl-DNA-specific enzyme known. To understand these novel properties, we solved cryo-EM structures of CnDNMT5 in three states. These studies reveal an elaborate allosteric cascade in which hemimethylated DNA binding first activates the SNF2 ATPase domain by a large rigid body rotation while the target cytosine partially flips out of the DNA duplex. ATP binding then triggers striking structural reconfigurations of the methyltransferase catalytic pocket to enable cofactor binding, completion of base flipping, and catalysis. Bound unmethylated DNA does not open the catalytic pocket and is instead ejected upon ATP binding, driving high fidelity. This unprecedented chaperone-like, enzyme-remodeling role of the SNF2 ATPase domain illuminates how energy is used to enable faithful epigenetic memory.

Indexed as

Adenosine TriphosphateEpigenomeAdenosine TriphosphatasesCytosineDNADNA MethylationMethyltransferasesAdenosine TriphosphatasesAdenosine TriphosphateCytosineDNAMethyltransferasesATPcryo-EM structureCryptococcus neoformansDNA cytosine-5 methyltransferaseDNA methylationDNMT5SAHSAMSNF2 ATPase

Identifiers

PMID35202575
PMCPMC8956514
OpenAlexW4212852230

What OpenQuestion holds

Textmetadata
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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.