PXD071242-1

PXD071242 is an original dataset announced via ProteomeXchange.

Title	ATM promotes reversed fork processing during DNA interstrand cross-link repair
Description	During replication-coupled DNA interstrand cross-link (ICL) repair, fork reversal is thought to enable the Fanconi anemia (FA) pathway to resolve the ICL through nucleolytic incisions. Subsequent fork restoration then allows nascent DNA strand extension past the lesion. Although these fork remodeling events are crucial for ICL repair, their regulation remains poorly understood. Here, we use cell-free Xenopus egg extracts and human cells to investigate fork dynamics during ICL repair by the FA pathway. We find that the ataxia telangiectasia-mutated (ATM) kinase is activated concomitantly with fork reversal and promotes resection of the reversed fork intermediate, in part by modulating nuclease association with chromatin. This resection depends on the coordinated activities of the EXO1 and DNA2 nucleases. We further show that the inhibition of protein phosphatase 2A (PP2A) during ICL repair results in ATM hyperactivation, reversed fork over-resection, and formation of aberrant end-joining products, indicating that PP2A counteracts ATM signaling to constrain reversed fork resection. Taken together, this work implicates reversed forks as substrates for ATM activation and reveals a phospho-regulatory circuit that governs reversed fork processing during ICL repair.
HostingRepository	PRIDE
AnnounceDate	2026-08-25
AnnouncementXML	Submission_2026-08-24_19:35:04.247.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: NEWT:8355;
ModificationList	phosphorylated residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-25 18:49:42	ID requested
⏵ 1	2026-08-24 19:35:04	announced

Dataset with its publication pending

submitter keyword: fork reversal, interstrand cross-link, EXO1, ICL repair, PP2A, Fanconi anemia pathway, DNA2,ATM, fork restoration, Orbitrap Astral mass spectrometer, WRN

Tsui-Fen Chou
contact affiliation	Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
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. PXD071242
     1. Label: PRIDE project
     2. Name: ATM promotes reversed fork processing during DNA interstrand cross-link repair