PXD051449

PXD051449 is an original dataset announced via ProteomeXchange.

Title	CFAP20 accelerates RNAPII elongation from promoters to prevent conflicts with co-directional replisomes
Description	Fine-tuning the coexistence of DNA replication and transcription is essential to avoid detrimental collisions between these two machineries. This is particularly relevant at promoters, as RNA polymerase II (RNAPII) elongation is slowest there, and DNA replication evolutionarily initiates in close proximity to these sites. The mechanisms that regulate the acceleration of RNAPII to specifically avoid conflicts with the incoming replisome in a co-directional manner have not been addressed. In this study, using genome-wide and proteomics approaches, we identify and characterize CFAP20 as part of a protective pathway that accelerates elongating RNAPII, diverting it from the path of co-directional replisomes. CFAP20-deficient cells accumulate R-loops specifically at promoters and display defects in origin firing and replication fork progression. Co-depletion of the Mediator complex, or removal of RNAPII engaged with R-loops, completely rescues these replication phenotypes. Therefore, we propose that CFAP20 aids in RNAPII acceleration under conditions of high Mediator-driven transcription output to fine-tune RNAPII elongation and prevent collisions with co-directional replisomes.
HostingRepository	PRIDE
AnnounceDate	2026-03-02
AnnouncementXML	Submission_2026-03-01_16:29:22.194.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD051449
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Nila Overbeek
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-15 07:07:27	ID requested
⏵ 1	2026-03-01 16:29:23	announced

Uruci S, Boer DEC, Chrystal PW, Lalonde M, Panagopoulos A, Yakoub G, Kird, ö, k I, de Lint K, van der Woude M, Wendel TJ, Brussee SJ, Wondergem AP, van Overbeek NK, Schotman N, Lingeman J, Ljungman M, van Oudenaarden A, van Attikum H, Vertegaal ACO, Noordermeer SM, Wolthuis RMF, Altmeyer M, Hamperl S, Tropepe V, van den Berg J, van den Heuvel D, Luijsterburg MS, CFAP20 salvages arrested RNAPII from the path of co-directional replisomes. Nature, 650(8103):1025-1034(2026) [pubmed]

10.6019/PXD051449;

10.1038/s41586-025-09943-7;

submitter keyword: Mediator, transcription-replication conflicts,CFAP20

Martijn S.
contact affiliation	Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
contact email	m.luijsterburg@lumc.nl
lab head
Nila Overbeek
contact affiliation	LUMC
contact email	n.k.van_overbeek@lumc.nl
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/2026/03/PXD051449

PRIDE project URI

• PRIDE
  1. PXD051449
     1. Label: PRIDE project
     2. Name: CFAP20 accelerates RNAPII elongation from promoters to prevent conflicts with co-directional replisomes