PXD017940

PXD017940 is an original dataset announced via ProteomeXchange.

Title	Two siblings with strong NER inactivation due to inherited ERCC1 deficiency display mild clinical features of XP and CS with severe liver impairment
Description	The ERCC1-XPF heterodimer is a multifunctional endonuclease involved in nucleotide excision repair (NER), inter-strand crosslink (ICL) repair, and DNA double-strand break (DSB) repair. Only two patients with inherited ERCC1 defects have been reported who both died at an early age. Here, we describe a new case of ERCC1 deficiency in two siblings (11 and 13 years) who show mild features of Xeroderma Pigmentosum and Cockayne Syndrome. Both patients displayed microcephaly, mild developmental delay, mild photosensitivity, and severe cholestatic liver problems. Genetic analysis revealed a maternal deletion and a paternal missense variant in ERCC1 (R156W) that affect a salt bridge just below the XPA-binding pocket. Studies in patient-derived fibroblasts and reconstituted knockout cells confirmed that mutant ERCC1 is not efficiently recruited to the NER complex due to a decreased interaction with XPA. Consequently, patient cells show a strong NER defect, although residual repair could be detected. The steady-state protein levels of ERCC1 and XPF were severely reduced in patient cells, but this only led to a mild defect in ICL repair, and no impact on DSB repair. We report a new case of ERCC1 deficiency that particularly affect NER and has only a mild impact on other ERCC1-dependent repair pathways.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:18:13.177.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Román González-Prieto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-09 04:06:14	ID requested
1	2021-01-26 04:39:40	announced
⏵ 2	2024-10-22 05:18:14	announced	2024-10-22: Updated project metadata.

10.1084/jem.20200622;

Apelt K, White SM, Kim HS, Yeo JE, Kragten A, Wondergem AP, Rooimans MA, Gonz, á, lez-Prieto R, Wiegant WW, Lunke S, Flanagan D, Pantaleo S, Quinlan C, Hardikar W, van Attikum H, Vertegaal ACO, Wilson BT, Wolthuis RMF, Sch, ä, rer OD, Luijsterburg MS, ERCC1 mutations impede DNA damage repair and cause liver and kidney dysfunction in patients. J Exp Med, 218(3):(2021) [pubmed]

submitter keyword: Nucleotide Excission Repair,ERCC1, Cockayne Syndrome, Xeroderma Pigmentosum

Alfred C.O. Vertegaal
contact affiliation	Cell and Chemical Biology Leiden University Medical Center Leiden, The Netherlands
contact email	vertegaal@lumc.nl
lab head
Román González-Prieto
contact affiliation	Andalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville
contact email	R.Gonzalez_Prieto@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/2021/01/PXD017940

PRIDE project URI

• PRIDE
  1. PXD017940
     1. Label: PRIDE project
     2. Name: Two siblings with strong NER inactivation due to inherited ERCC1 deficiency display mild clinical features of XP and CS with severe liver impairment