PXD055646-1

PXD055646 is an original dataset announced via ProteomeXchange.

Title	The Fanconi anemia pathway repairs colibactin-induced DNA interstrand cross-links
Description	Colibactin is a secondary metabolite produced by bacteria present in the human gut and is implicated in the progression of colorectal cancer and inflammatory bowel disease. This genotoxin alkylates deoxyadenosines on opposite strands of host cell DNA to produce DNA interstrand cross-links (ICLs) that block DNA replication. While cells have evolved multiple mechanisms to resolve (“unhook”) ICLs encountered by the replication machinery, little is known about which of these pathways promote resistance to colibactin-induced ICLs. Here, we use Xenopus egg extracts to investigate replication-coupled repair of plasmids engineered to contain site-specific colibactin-ICLs. We show that replication fork stalling at a colibactin-ICL leads to replisome disassembly and activation of the Fanconi anemia ICL repair pathway, which unhooks the colibactin-ICL through nucleolytic incisions. These incisions generate a DNA double-strand break intermediate in one sister chromatid, which can be repaired by homologous recombination, and a monoadduct (“ICL remnant”) in the other. Our data indicate that translesion synthesis past the colibactin-ICL remnant depends on Pol-ita and the Pol-kappa-REV1-Pol-Zitapolymerase complex. Although translesion synthesis past colibactin-induced DNA damage is frequently error-free, it can introduce T>N point mutations that partially recapitulate the mutation signature associated with colibactin exposure in vivo. Taken together, our work provides a molecular framework for understanding how cells tolerate a naturally occurring and clinically relevant ICL.
HostingRepository	PRIDE
AnnounceDate	2025-09-11
AnnouncementXML	Submission_2025-09-10_21:21:30.697.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ting-Yu Wang
SpeciesList	scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-06 16:25:27	ID requested
⏵ 1	2025-09-10 21:21:31	announced

Dataset with its publication pending

submitter keyword: interstrand cross-link, colibactin,xenopus laevis

Tsui-Fen Chou
contact affiliation	Proteome Exploration Laboratory
contact email	tfchou@caltech.edu
lab head
Ting-Yu Wang
contact affiliation	Caltech
contact email	tywang@caltech.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055646
     1. Label: PRIDE project
     2. Name: The Fanconi anemia pathway repairs colibactin-induced DNA interstrand cross-links