Evidence map›Paper›PMID 42230560›Full record

ArticleNature communications2026

Structural basis for uracil removal from DNA by human SMUG1.

Julian M Ludäscher, Emma Scaletti Hutchinson, Guillem Vila-Julià, Ann-Sofie Jemth, Saher Shahid, Elisee Wiita, Israel Cabeza de Vaca, Szymon Pach, Lukas Gajdos, Swati Aggarwal and 5 more

Abstract read
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. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

15 authors.

Julian M LudäscherDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.ORCID 0009-0005-7242-5133
Emma Scaletti HutchinsonDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Guillem Vila-JuliàScience for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.ORCID 0000-0001-5576-7442
Ann-Sofie JemthScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0002-7550-1833
Saher ShahidDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Elisee WiitaScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
Israel Cabeza de VacaScience for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-6208-1091
Szymon PachScience for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Lukas GajdosLarge Scale Structures group, Institut Laue-Langevin (ILL), Grenoble, France.ORCID 0000-0002-9377-1677
Swati AggarwalEuropean Spallation Source (ESS), Lund, Sweden.
Ellen WalseDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Oliver MortusewiczScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0002-4290-4994
Thomas HelledayScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0002-7384-092X
Jens CarlssonScience for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.ORCID 0000-0003-4623-2977
Pål StenmarkDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden. stenmark@dbb.su.se.ORCID 0000-0003-4777-3417

Funding

Barncancerfonden (Swedish Childhood Cancer Foundation) 2024-0048Cancerfonden (Swedish Cancer Society) 24-3694, 22 2473 Pj, 25 4860 Pj and 24 3848 PjVetenskapsrådet (Swedish Research Council) 2015-00162 and 2022-03681
6 · The paper itself

Abstract

Human single-strand-selective monofunctional uracil DNA glycosylase 1 (hSMUG1) removes uracil, 5-hydroxymethyluracil (5hmU) and 5-fluorouracil (5FU) from DNA, thereby initiating the base excision repair (BER) process. hSMUG1 is important for maintaining genomic integrity and plays a significant role in cancer biology. Here, we present the structures of hSMUG1, including complexes with products (uracil and 5FU) and an enzyme-product complex of hSMUG1 with double-stranded DNA (dsDNA). Analysis of our hSMUG1-dsDNA complex reveals how uracil is flipped out of the dsDNA for excision and identifies key residues that we confirm to be critical for both DNA binding and enzymatic activity. Furthermore, our hSMUG1 substrate complexes, molecular dynamics simulations and neutron diffraction data suggest a mechanism by which the substrate uracil rotates following base excision. The structural and functional information presented here will be highly useful for the future development of inhibitors and/or activators targeting hSMUG1.

Indexed as

DNAUracilUracil-DNA GlycosidaseCrystallography, X-RayDNA RepairExcision RepairFluorouracilHumansMolecular Dynamics SimulationPentoxylProtein Binding5-hydroxymethyluracilDNAFluorouracilPentoxylSMUG1 protein, humanUracilUracil-DNA Glycosidase

Identifiers

PMID42230560
PMCPMC13230825

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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.