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The relationships between XPC binding to conformationally diverse DNA adducts and their excision by the human NER system: is there a correlation?
- Source :
-
DNA repair [DNA Repair (Amst)] 2014 Jul; Vol. 19, pp. 55-63. Date of Electronic Publication: 2014 Apr 29. - Publication Year :
- 2014
-
Abstract
- The first eukaryotic NER factor that recognizes NER substrates is the heterodimeric XPC-RAD23B protein. The currently accepted hypothesis is that this protein recognizes the distortions/destabilization caused by DNA lesions rather than the lesions themselves. The resulting XPC-RAD23B-DNA complexes serve as scaffolds for the recruitment of subsequent NER factors that lead to the excision of the oligonucleotide sequences containing the lesions. Based on several well-known examples of DNA lesions like the UV radiation-induced CPD and 6-4 photodimers, as well as cisplatin-derived intrastrand cross-linked lesions, it is generally believed that the differences in excision activities in human cell extracts is correlated with the binding affinities of XPC-RAD23B to these DNA lesions. However, using electrophoretic mobility shift assays, we have found that XPC-RAD23B binding affinities of certain bulky lesions derived from metabolically activated polycyclic aromatic hydrocarbon compounds such as benzo[a]pyrene and dibenzo[a,l]pyrene, are not directly, or necessarily correlated with NER excision activities observed in cell-free extracts. These findings point to features of XPC-RAD23B-bulky DNA adduct complexes that may involve the formation of NER-productive or unproductive forms of binding that depend on the structural and stereochemical properties of the DNA adducts studied. The pronounced differences in NER cleavage efficiencies observed in cell-free extracts may be due to differences in the successful recruitment of subsequent NER factors by the XPC-RAD23B-DNA adduct complexes, and/or in the verification step. These phenomena appear to depend on the structural and conformational properties of the class of bulky DNA adducts studied.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Subjects :
- Benzopyrenes pharmacology
Cisplatin pharmacology
DNA Adducts biosynthesis
DNA Damage drug effects
DNA Damage genetics
DNA Damage radiation effects
DNA Repair drug effects
DNA Repair radiation effects
DNA Repair Enzymes biosynthesis
DNA Repair Enzymes chemistry
DNA-Binding Proteins biosynthesis
DNA-Binding Proteins chemistry
Humans
Nucleic Acid Conformation drug effects
Nucleic Acid Conformation radiation effects
Protein Binding
Protein Conformation drug effects
Protein Conformation radiation effects
Ultraviolet Rays
DNA Adducts genetics
DNA Repair genetics
DNA Repair Enzymes genetics
DNA-Binding Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1568-7856
- Volume :
- 19
- Database :
- MEDLINE
- Journal :
- DNA repair
- Publication Type :
- Academic Journal
- Accession number :
- 24784728
- Full Text :
- https://doi.org/10.1016/j.dnarep.2014.03.026