Generation of DNA single-strand displacement by compromised nucleotide excision repair

Autor: Camille, Godon, Sophie, Mourgues, Julie, Nonnekens, Amandine, Mourcet, Fréderic, Coin, Wim, Vermeulen, Pierre-Olivier, Mari, Giuseppina, Giglia-Mari
Přispěvatelé: Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Molecular Genetics, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Coin, Frédéric
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: EMBO Journal
EMBO Journal, EMBO Press, 2012, 31 (17), pp.3550-3563. ⟨10.1038/emboj.2012.193⟩
EMBO Journal, 31(17), 3550-3563. Wiley-Blackwell
The EMBO Journal
The EMBO Journal, 2012, 31 (17), pp.3550-3563. ⟨10.1038/emboj.2012.193⟩
ISSN: 0261-4189
1460-2075
DOI: 10.1038/emboj.2012.193⟩
Popis: Nucleotide excision repair (NER) is a precisely coordinated process essential to avoid DNA damage-induced cellular malfunction and mutagenesis. Here, we investigate the mechanistic details and effects of the NER machinery when it is compromised by a pathologically significant mutation in a subunit of the repair/transcription factor TFIIH, namely XPD. In contrast to previous studies, we find that no single- or double-strand DNA breaks are produced at early time points after UV irradiation of cells bearing a specific XPD mutation, despite the presence of a clear histone H2AX phosphorylation (cH2AX) signal in the UV-exposed areas. We show that the observed cH2AX signal can be explained by the presence of longer single-strand gaps possibly generated by strand displacement. Our in vivo measurements also indicate a strongly reduced TFIIH-XPG binding that could promote single-strand displacement at the site of UV lesions. This finding not only highlights the crucial role of XPG's interactions with TFIIH for proper NER, but also sheds new light on how a faulty DNA repair process can induce extreme genomic instability in human patients. The EMBO Journal (2012) 31, 3550-3563. doi: 10.1038/emboj.2012.193; Published online 3 August 2012 Subject Categories: genome stability & dynamics; molecular biology of disease
Databáze: OpenAIRE
Externí odkaz: