Details
- Autor(en) / Beteiligte
- Titel
- The relationships between XPC binding to conformationally diverse DNA adducts and their excision by the human NER system: Is there a correlation?
- Ist Teil von
- DNA repair, 2014-07, Vol.19, p.55-63
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- Elsevier ScienceDirect Journals Complete
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1568-7864eISSN: 1568-7856DOI: 10.1016/j.dnarep.2014.03.026Titel-ID: cdi_pubmed_primary_24784728
- Format
- –
- Schlagworte
- Benzo[a]pyrene, Benzopyrenes - pharmacology, Cisplatin - pharmacology, Dibenzo[a,l]pyrene, DNA adduct, DNA Adducts - biosynthesis, DNA Adducts - genetics, DNA Damage - drug effects, DNA Damage - genetics, DNA Damage - radiation effects, DNA Repair - drug effects, DNA Repair - genetics, DNA Repair - radiation effects, DNA Repair Enzymes - biosynthesis, DNA Repair Enzymes - chemistry, DNA Repair Enzymes - genetics, DNA-Binding Proteins - biosynthesis, DNA-Binding Proteins - chemistry, DNA-Binding Proteins - genetics, Electrophoretic mobility shift assay, Humans, Nucleic Acid Conformation - drug effects, Nucleic Acid Conformation - radiation effects, Nucleotide excision repair (NER), Protein Binding, Protein Conformation - drug effects, Protein Conformation - radiation effects, Ultraviolet Rays, XPC-RAD23B binding