We have studied the reaction pathways of guanine radicals in DNA in aqueous solution.  Among the different lesions formed are  the stereoisomeric Spiroiminodihydantoin (Sp) lesions and the recently discovered intrastrand cross-linked G*-T* and G*CT* lesions characterized by a covalent G(C8)-T(N3) bond (C. Crean et al, Nucl. Acids. Res. 36:742, 2008).  We investigated the repair of these oxidatively generated lesions in cell-free extracts from human HeLa cells.  All three are substrates of both nucleotide excision repair (NER) and base excision repair (BER).  While both the Sp lesions, as well as the intrastrand cross-linked G*CT* lesion are medium to excellent substrates of NER,  the strand with the G*T* cross-linked product is only weakly incised. Typically, the levels of  BER excision products rise rapidly within the first ~ 5 � 10  min of incubation and then reach a constant level, while the levels of the typical NER 24-30-mer DNA fragments  increase approximately linearly with time at least up to 40 min.  Our hypothesis is that the NER system may function as a backup for BER.  Supported by NIEHS Grants ES 011589, and by CA 099194.

Competitive removal of oxidatively generated guanine lesions in DNA by NER and BER in human cell extracts

240th National Meeting (2010)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.