Coordination of dual incision and repair synthesis in human nucleotide excision repair
| Autor: | Jacqueline H. Enzlin, Adebanke F. Fagbemi, Giuseppina Giglia-Mari, Wim Vermeulen, Stuart G. Clarkson, Lidija Staresincic, Audrey M. Gourdin, Isabelle Dunand-Sauthier, Orlando D. Schärer, Nils Wijgers |
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| Přispěvatelé: | University of Geneva Medical School, Department of Pathology and Immunology, Molecular Genetics |
| Rok vydání: | 2009 |
| Předmět: |
DNA Repair
Endonucleases/genetics/metabolism ddc:616.07 Transcription Factors/genetics/metabolism chemistry.chemical_compound 0302 clinical medicine Catalytic Domain ComputingMilieux_MISCELLANEOUS Genetics 0303 health sciences biology General Neuroscience Nuclear Proteins DNA/genetics/*metabolism/radiation effects Cell biology DNA-Binding Proteins Proliferating Cell Nuclear Antigen/genetics/metabolism 030220 oncology & carcinogenesis Xeroderma pigmentosum DNA repair DNA damage Ultraviolet Rays DNA Damage DNA Single-Stranded DNA-binding protein Article General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Proliferating Cell Nuclear Antigen medicine Animals Humans Nuclear Proteins/genetics/metabolism Molecular Biology 030304 developmental biology General Immunology and Microbiology Oligonucleotide [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology DNA Endonucleases medicine.disease Proliferating cell nuclear antigen chemistry DNA-Binding Proteins/genetics/metabolism biology.protein DNA Single-Stranded/metabolism Transcription Factors Nucleotide excision repair |
| Zdroj: | EMBO Journal EMBO Journal, EMBO Press, 2009, 28 (8), pp.1111-1120. ⟨10.1038/emboj.2009.49⟩ EMBO Journal, Vol. 28, No 8 (2009) pp. 1111-1120 EMBO Journal, 28(8), 1111-1120. Wiley-Blackwell |
| ISSN: | 0261-4189 1460-2075 |
| DOI: | 10.1038/emboj.2009.49 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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