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PXD017940

PXD017940 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTwo siblings with strong NER inactivation due to inherited ERCC1 deficiency display mild clinical features of XP and CS with severe liver impairment
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:18:13.177.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRomán González-Prieto
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-03-09 04:06:14ID requested
12021-01-26 04:39:40announced
22024-10-22 05:18:14announced2024-10-22: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: Nucleotide Excission Repair,ERCC1, Cockayne Syndrome, Xeroderma Pigmentosum
Contact List
Alfred C.O. Vertegaal
contact affiliationCell and Chemical Biology Leiden University Medical Center Leiden, The Netherlands
contact emailvertegaal@lumc.nl
lab head
Román González-Prieto
contact affiliationAndalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville
contact emailR.Gonzalez_Prieto@lumc.nl
dataset submitter
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Dataset FTP location
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