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 (Articolo in rivista)

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Label
  • 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 (Articolo in rivista) (literal)
Anno
  • 2003-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1093/hmg/ddg174 (literal)
Alternative label
  • Rapic-Otrin V, Navazza V, Nardo T, Botta E, McLenigan M, Bisi DC, Levine AS, Stefanini M. (2003)
    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
    in Human molecular genetics (Print); Oxford University Press, Oxford (Regno Unito)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Rapic-Otrin V, Navazza V, Nardo T, Botta E, McLenigan M, Bisi DC, Levine AS, Stefanini M. (literal)
Pagina inizio
  • 1507 (literal)
Pagina fine
  • 1522 (literal)
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  • 12 (literal)
Rivista
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  • The first two authors should be regarded as joint First Authors. Impact Factor: 8.597 (literal)
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  • Oltre a chiarire la relazione genotipo-fenotipo nel gruppo E dello xeroderma pigmentosum, questo studio ha fornito un contributo alla comprensione del ruolo dell’attività DNA damage-binding protein (DDB) nella riparazione del DNA. La rilevanza di questi risultati è stata commentata in: HOT TOPICS IN DNA REPAIR NO. 7 (Wittschieben B and Wood RD. DDB complexities. DNA Repair, 2:1065-1069, 2003) e in HOTSPOTS IN CLINICAL GENETICS (Andrew SE. Redefining xeroderma pigmentosum complementation group E. Clin Genet, 64: 294–295, 2003). (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • Rapic-Otrin V. (1)*, Navazza V. (2)*, Nardo T. (2), Botta E. (2), McLenigan M. (3), Bisi D.(1), Levine A. (1) and M. Stefanini (2). *The first two authors should be regarded as joint First Authors. 1) Dept. of Molecular Genetics and Biochemistry, School of Medicine and Cancer Institute, University of Pittsburgh, USA. 2) Istituto di Genetica Molecolare CNR, Pavia, Italy. 3) National Institute of Child Health and Human Development, NIH, Bethesda, USA. (literal)
Titolo
  • 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 (literal)
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 phenotype is DDB_, resulting from defects in a single gene, DDB2, our results identify the functional domains of the corresponding p48 protein. (literal)
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