The UV-damaged DNA binding protein mediates efficient targeting of the nucleotide excision repair complex to UV-induced photo lesions

J Moser, M Volker, H Kool, S Alekseev, H Vrieling, A Yasui, AA van Zeeland, LHF Mullenders*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

138 Citations (Scopus)

Abstract

Previous studies point to the XPC-hHR23B complex as the principal initiator of global genome nucleotide excision repair (NER) pathway, responsible for the repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) in human cells. However, the UV-damaged DNA binding protein (UV-DDB) has also been proposed as a damage recognition factor involved in repair of UV-photoproducts, especially CPD. Here, we show in human XP-E cells (UV-DDB deficient) that the incision complex formation at UV-induced lesions was severely diminished in locally damaged nuclear spots. Repair kinetics of CPD and 6-4PP in locally and globally UV-irradiated normal human and XP-E cells demonstrate that UV-DDB can mediate efficient targeting of XPC-hHR23B and other NER factors to 6-4PR The data is consistent with a mechanism in which UV-DDB forms a stable complex when bound to a 6-4PP, allowing subsequent repair proteins starting with XPC-hHR23B - to accumulate, and verify the lesion, resulting in efficient 6-4PP repair. These findings suggest that (i) UV-DDB accelerates repair of 6-4PP, and at later time points also CPD, (ii) the fraction of 6-4PP that can be bound by UV-DDB is limited due to its low cellular quantity and fast UV dependent degradation, and (iii) in the absence of UV-DDB a slow XPC-hHR23B dependent pathway is capable to repair 6-4PP, and to some extent also CPD. (c) 2005 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)571-582
Number of pages12
JournalDna repair
Volume4
Issue number5
DOIs
Publication statusPublished - 2-May-2005

Keywords

  • UV-damaged DNA binding protein
  • xeroderma pigmentosum group E
  • 6-4 photoproducts
  • cylcobutane pyrimidine dimmers
  • nucleotide excision repair
  • PIGMENTOSUM GROUP-E
  • CYCLOBUTANE PYRIMIDINE DIMERS
  • GLOBAL GENOMIC REPAIR
  • GROUP-E CELLS
  • IN-VIVO
  • GENE-PRODUCT
  • P48 SUBUNIT
  • DDB2 GENE
  • IRRADIATION
  • XPC

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