True XP group E patients have a defective UV-damaged DNA binding protein complex and mutations in DDB2 which reveal the functional domains of its p48 product
Abstract
Xeroderma pigmentosum (XP) is a skin cancer-prone autosomal recessive disease characterized by inability to repair UV-induced DNA damage. The major form of XP is defective in nucleotide excision repair (NER) and comprises seven complementation groups (A-G). The genes defective in all groups have been identified unambiguously with the exception of group E. The cells of some XP-E patients are deficient in a protein complex (consisting of two subunits: p127/DDBI and p48/DDB2) which binds to UV-damaged DNA (UV-DDB) and is specifically involved in the removal of photoproducts from the non-transcribed regions of the genome. However, other XP-E patients have been reported not to lack UV-damaged DNA binding activity (DDB(+)). Here we describe several genetically unrelated XP-E patients, not previously analyzed in depth, each carrying two mutated alleles for DDB2, causing either a single amino acid change or a protein truncation or internal deletion. These defects result in a severe decrease of detectable p48 protein, abolish interaction with the p127 subunit, and produce a deficiency in UV-DDB binding activity (DDB(-)). The role of p48 in the repair defect of these patients was demonstrated in vivo and in vitro. Investigation of four DDB(+) cell strains from patients previously assigned to XP-E, allowed us to reclassify all of them into other groups and to show that they do not share the molecular and biochemical features typical for XP-E. Besides confirming that the true XP-E phenot…
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Mutations in human and mouse DDB2 compromise DNA repair and cause xeroderma pigmentosum, a disease characterized by hypersensitivity to sunlight.
“Mutations in human and mouse DDB2 compromise DNA repair and cause xeroderma pigmentosum48, a disease characterized by hypersensitivity to sunlight.”
From A genomics approach reveals insights into the importance of gene losses for mammalian adaptations (2018) · cites this paper as [48]
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- Authors
- Rapic-Otrin, V.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-07-01
- Volume
- 12
- Issue
- 13
- Pages
- 1507-1522
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2156518131
- Cited by
- 113
- References
- 1
- Citations by year
- 2026: 2 · 2025: 4 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 6
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- DDB2, nucleotide excision repair, UV-induced DNA damage, complementation groups, functional domains, truncating mutations
- MeSH terms
- Adult, Alleles, Cell Nucleus, Cells, Cultured, DNA Mutational Analysis, DNA Repair, DNA-Binding Proteins, Dose-Response Relationship, Radiation, Exons, Female, Genotype, Humans, Male, Models, Genetic, Mutation, Phenotype, Precipitin Tests, Protein Binding, Ultraviolet Rays, Xeroderma Pigmentosum, Immunoblotting, Genome, Gene Deletion, Sequence Analysis, DNA, Protein Structure, Tertiary
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