Coordination of dual incision and repair synthesis in human nucleotide excision repair

Staresincic, Lidija; Fagbemi, Adebanke F.; Enzlin, Jacqueline H.; Gourdin, Audrey M.; Wijgers, Nils; Dunand-Sauthier, Isabelle; Giglia-Mari, Giuseppina; Clarkson, Stuart Gordon; Vermeulen, Wim; Scharer, Orlando D.

doi:10.1038/emboj.2009.49

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Title		Coordination of dual incision and repair synthesis in human nucleotide excision repair
Authors		Staresincic, Lidija Fagbemi, Adebanke F. Enzlin, Jacqueline H. Gourdin, Audrey M. Wijgers, Nils Dunand-Sauthier, Isabelle Giglia-Mari, Giuseppina Clarkson, Stuart Gordon Vermeulen, Wim Scharer, Orlando D. show all authors [1 - 10]
Published in		EMBO Journal. 2009, vol. 28, no. 8, p. 1111-1120
Abstract		Nucleotide excision repair (NER) requires the coordinated sequential assembly and actions of the involved proteins at sites of DNA damage. Following damage recognition, dual incision 5' to the lesion by ERCC1-XPF and 3' to the lesion by XPG leads to the removal of a lesion-containing oligonucleotide of about 30 nucleotides. The resulting single-stranded DNA (ssDNA) gap on the undamaged strand is filled in by DNA repair synthesis. Here, we have asked how dual incision and repair synthesis are coordinated in human cells to avoid the exposure of potentially harmful ssDNA intermediates. Using catalytically inactive mutants of ERCC1-XPF and XPG, we show that the 5' incision by ERCC1-XPF precedes the 3' incision by XPG and that the initiation of repair synthesis does not require the catalytic activity of XPG. We propose that a defined order of dual incision and repair synthesis exists in human cells in the form of a 'cut-patch-cut-patch' mechanism. This mechanism may aid the smooth progression through the NER pathway and contribute to genome integrity.
Keywords		Animals — Catalytic Domain — Cell Line — DNA/genetics/metabolism/radiation effects — DNA Damage — *DNA Repair — DNA, Single-Stranded/metabolism — DNA-Binding Proteins/genetics/metabolism — Endonucleases/genetics/metabolism — Humans — Nuclear Proteins/genetics/metabolism — Proliferating Cell Nuclear Antigen/genetics/metabolism — Transcription Factors/genetics/metabolism — Ultraviolet Rays
Identifiers		DOI: 10.1038/emboj.2009.49 PMID: 19279666
Full text		Article - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683701/pdf/emboj200949a.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Groupe Reith Walter (pathologie et immunologie) (282)
Citation (ISO format)		STARESINCIC, Lidija et al. Coordination of dual incision and repair synthesis in human nucleotide excision repair. In: EMBO Journal, 2009, vol. 28, n° 8, p. 1111-1120. https://archive-ouverte.unige.ch/unige:20116