Evidence map›Paper›PMID 40501905›Full record

ArticlebioRxiv : the preprint server for biology2025

The specificity and structure of DNA crosslinking by the gut bacterial genotoxin colibactin.

Erik S Carlson, Raphael Haslecker, Chiara Lecchi, Miguel A Aguilar Ramos, Vyshnavi Vennelakanti, Linda Honaker, Alessia Stornetta, Estela S Millán, Bruce A Johnson, Heather J Kulik and 4 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Erik S CarlsonDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0001-9134-1246
Raphael HasleckerDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0001-8001-9534
Chiara LecchiMasonic Cancer Center University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0009-0009-0345-778X
Miguel A Aguilar RamosDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0002-2537-8371
Vyshnavi VennelakantiDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0001-7677-2902
Linda HonakerDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Alessia StornettaMasonic Cancer Center University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-8287-9551
Estela S MillánDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0009-0001-4096-853X
Bruce A JohnsonStructural Biology Initiative, City University of New York (CUNY) Advanced Science Research Center, New York, NY 10031, USA.ORCID 0000-0001-8445-5368
Heather J KulikDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0001-9342-0191
Silvia BalboMasonic Cancer Center University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-7686-0504
Peter W VillaltaMasonic Cancer Center University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-0067-3083
Victoria D'SouzaDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0002-5397-9481
Emily P BalskusDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0001-5985-5714

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
Understanding the Mechanism of a Gut Microbial Genotoxin Involved in Colorectal CarcinogenesisR01CA208834 · NCI · HARVARD UNIVERSITY · PI BALSKUS, EMILY PATRICIA · 2016 to 2025
$3.7M
NMRFx: An Integrated software suite for macromolecular NMR analysisR01GM123012 · NIGMS · ADVANCED SCIENCE RESEARCH CENTER · PI JOHNSON, BRUCE A · 2017 to 2025
$2.6M
Mass Spectrometric Analytical Collaborations with Members of the Masonic Cancer Center of the University of MinnesotaR50CA211256 · NCI · UNIVERSITY OF MINNESOTA · PI Peter William Villalta · 2016 to 2026
$2.1M
Revealing Nature's Blueprints for Single-Site Catalysis of C-H Activation with First-principles Modeling and Machine LearningR35GM152027 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Heather J. Kulik · 2024 to 2026
$1.2M
Deciphering the mechanism of colibactin-induced DNA damage through quantitative and biochemical approachesF32CA254165 · NCI · HARVARD UNIVERSITY · PI CARLSON, ERIK S · 2020 to 2022
$179k
NCI NIH HHS F32 CA254165NCI NIH HHS P30 CA077598NCI NIH HHS R01 CA208834NCI NIH HHS R50 CA211256NIGMS NIH HHS R01 GM123012NIGMS NIH HHS R35 GM152027
6 · The paper itself

Abstract

Accumulating evidence has connected the chemically unstable, DNA-damaging gut bacterial natural product colibactin to colorectal cancer, including the identification of mutational signatures that are thought to arise from colibactin-DNA interstrand crosslinks (ICLs). However, we currently lack direct information regarding the structure of this lesion. Here, we combine mass spectrometry and nuclear magnetic resonance spectroscopy to elucidate the specificity and structure of the colibactin-DNA ICL. We find that colibactin alkylates within the minor groove of AT-rich DNA, explaining the origins of mutational signatures. Unexpectedly, we discover that the chemically unstable central motif of colibactin mediates the sequence specificity of crosslinking. By directly elucidating colibactin's interactions with DNA, this work enhances our understanding of the structure and genotoxic mechanisms of this cancer-linked gut bacterial natural product.

Identifiers

PMID40501905
PMCPMC12154741

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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.