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Coordination of dual incision and repair synthesis in human nucleotide excision repair
Author(s) -
Staresincic Lidija,
Fagbemi Adebanke F,
Enzlin Jacqueline H,
Gourdin Audrey M,
Wijgers Nils,
DunandSauthier Isabelle,
GigliaMari Giuseppina,
Clarkson Stuart G,
Vermeulen Wim,
Schärer Orlando D
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.49
Subject(s) - nucleotide excision repair , biology , ercc1 , dna damage , dna repair , oligonucleotide , dna , lesion , microbiology and biotechnology , genetics , pathology , medicine
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.