PXD045654-1

PXD045654 is an original dataset announced via ProteomeXchange.

Title	The CGG triplet repeat binding protein 1 counteracts DNA secondary structure formation to prevent transcription-replication stress
Description	Short tracts of trinucleotide repeats with less than 10 repeats are found frequently throughout the genome without any apparent negative impact on DNA replication fork progression or transcription elongation. CGG binding protein 1 (CGGBP1) binds to CGG triplet repeats and has been implicated in multiple cellular processes such as transcription, replication and DNA damage. Here, we show that CGGBP1 binds to human gene promoter sites with short CGG repeat tracts prone to G-quadruplex and R-loop secondary structure formation. Depletion of CGGBP1 in human cells leads to substantial transcriptomic changes which coincides with increased replication fork stalling and transcription-replication conflicts. Consistently, an episomal model locus as well as endogenous candidate genes containing short tracts of CGG repeats show R-loop accumulation and increased RNAPII chromatin occupancy in CGGBP1-depleted cells. Mass spectrometry identifies the DEAD-box helicase DDX41 as a specific interaction partner of CGGBP1, thereby providing mechanistic insight how CGGBP1 can counteract the formation of secondary DNA structures at CGG repeats. Together, our work shows that short trinucleotide repeats are a source of genome-destabilizing secondary structures and cells rely on specific DNA-binding factors to maintain proper transcription and replication progression at short trinucleotide repeats.
HostingRepository	PRIDE
AnnounceDate	2025-10-20
AnnouncementXML	Submission_2025-10-19_16:30:48.565.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ann-Christine König
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-25 06:40:00	ID requested
⏵ 1	2025-10-19 16:30:49	announced

10.1038/s44319-025-00550-1;

Ummethum H, Murriello AC, Werner M, M, á, rquez-G, ó, mez E, K, ö, nig AC, Kruse E, Lalonde M, Trauner M, Chanou A, Wei, β M, Lee CSK, Ettinger A, Erhard F, Hauck SM, Hamperl S, The CGG triplet repeat binding protein 1 counteracts R-loop induced transcription-replication stress. EMBO Rep, 26(19):4691-4722(2025) [pubmed]

submitter keyword: Transcription-Replication Conflicts, Genomic Instability, CGGBP1, R-loop structure,CGG-trinucleotide repeats, Replication Stress, Transcription Regulation, DNA damag, G-quadruplex structure

Stephan Hamperl
contact affiliation	Chromosome dynamics and genome stability, Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, Feodor-Lynen-Strasse 21, 81377 München, Germany
contact email	stephan.hamperl@helmholtz-munich.de
lab head
Ann-Christine König
contact affiliation	HMGU Core Facility Proteomics
contact email	ann-christine.koenig@helmholtz-muenchen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD045654

PRIDE project URI

• PRIDE
  1. PXD045654
     1. Label: PRIDE project
     2. Name: The CGG triplet repeat binding protein 1 counteracts DNA secondary structure formation to prevent transcription-replication stress