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Sequential assembly of the nucleotide excision repair factors in vivo

  • Marcel Volker
  • , Martijn J. Moné
  • , Parimal Karmakar
  • , Anneke Van Hoffen
  • , Wouter Schul
  • , Wim Vermeulen
  • , Jan H.J. Hoeijmakers
  • , Roel Van Driel
  • , Albert A. Van Zeeland
  • , Leon H.F. Mullenders

Research output: Contribution to journalArticlepeer-review

693 Citations (Scopus)

Abstract

Here, we describe the assembly of the nucleotide excision repair (NER) complex in normal and repair-deficient (xeroderma pigmentosum) human cells, employing a novel technique of local UV irradiation combined with fluorescent antibody labeling. The damage recognition complex XPC-hHR23B appears to be essential for the recruitment of all subsequent NER factors in the preincision complex, including transcription repair factor TFIIH. XPA associates relatively late, is required for anchoring of ERCC1-XPF, and may be essential for activation of the endonuclease activity of XPG. These findings identify XPC as the earliest known NER factor in the reaction mechanism, give insight into the order of subsequent NER components, provide evidence for a dual role of XPA, and support a concept of sequential assembly of repair proteins at the site of the damage rather than a preassembled repairosome.

Original languageEnglish
Pages (from-to)213-224
Number of pages12
JournalMolecular Cell
Volume8
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

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