PXD033520 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A disease-associated XPA allele interferes with TFIIH binding and primarily affects the transcription-coupled sub-pathway of nucleotide excision repair |
Description | XPA is a central scaffold protein in nucleotide excision repair (NER) that interacts with and coordinates the assembly of repair complexes. Inactivating mutations in XPA causes Xeroderma Pigmentosum (XP), which is characterized by extreme UV sensitivity and a highly elevated skin cancer risk. Here, we describe two Dutch siblings in their late forties carrying a homozygous H244R substitution in the C-terminus of XPA with a mild manifestation of XP without skin cancer, but with neurological features including cerebellar ataxia. We show that the mutant XPA protein shows a severely weakened interaction with the TFIIH complex leading to its inefficient association with NER complexes and an inability to support the efficient association of the ERCC1-XPF endonuclease with repair complexes. Despite these defects, we find that patient-derived fibroblasts and reconstituted knockout cells carrying the H244R substitution show considerable levels of residual global genome repair (~40%), which is in intrinsic property of the mutated protein as revealed by in vitro experiments. In contrast, patient fibroblasts and engineered cells only expressing the mutant XPA protein were fully deficient in transcription-coupled repair. We report a new case of XPA deficiency that interferes with TFIIH binding and primarily affects the transcription-coupled sub-pathway of nucleotide excision repair, which is more closely associated with neurological features than to skin abnormalities. |
HostingRepository | PRIDE |
AnnounceDate | 2023-02-19 |
AnnouncementXML | Submission_2023-02-19_14:40:01.463.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | RománGonzález-Prieto |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-04-28 01:22:47 | ID requested | |
⏵ 1 | 2023-02-19 14:40:01 | announced | |
2 | 2023-11-14 08:56:06 | announced | 2023-11-14: Updated project metadata. |
Publication List
Keyword List
submitter keyword: Nucleotide Excision Repair |
Xeroderma Pigmentosum |
Contact List
AlfredVertegaal |
contact affiliation | Cell and Chemical Biology LUMC The Netherlands |
contact email | vertegaal@lumc.nl |
lab head | |
RománGonzález-Prieto |
contact affiliation | Andalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville |
contact email | roman.gonzalez@cabimer.es |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD033520
- Label: PRIDE project
- Name: A disease-associated XPA allele interferes with TFIIH binding and primarily affects the transcription-coupled sub-pathway of nucleotide excision repair