Environmental and Molecular Mutagenesis (EMM) Editor’s Choice - May 2011
The Editor's Choice for May is “Divergent Effects of Oxidatively Induced Modification to the C8 of 2’-Deoxyadenosine on Transcription Factor Binding: 8,5’(S)-Cyclo-2’-deoxyadenosine Inhibits the Binding of Multiple Sequence Specific Transcription Factors, While 8-Oxo-2’-deoxyadenosine Increases Binding of CREB and NF-kappa B to DNA” by Jessy Abraham and Philip J. Brooks.
Oxidative stress is a major source of DNA damage. The research article by Drs. Abraham and Brooks investigated two types of damaged nucleosides, which occur in DNA exposed to oxidative stress. They synthesized oligonucleotides carrying damaged bases within DNA sequences known to function as transcription factor binding sites, then tested the ability of the transcription factors to bind the modified sequences. Specifically, they showed that 8,5’-cyclopurine-2’-deoxyadenosine, when present in the binding sites for transcription factors HSF1, CREB, or NF-kappa B, eliminated binding of the transcription factors to their respective target sequences. They postulate that this loss of binding occurs because the aberrant nucleoside distorts the transcription factor binding sites within the DNA.
On the other hand, Abraham and Brooks show for the first time that 8-oxo-7,8-dihydro-2’-deoxyadenosine (8-oxo-dA), within the appropriate target sequences, increased the binding of two transcription factors (NF-kappa B and CREB). The authors note that the increased binding efficiency may be explained by the formation of an additional hydrogen bond between the damaged base and an amino acid within the transcription factor. These results support the idea that 8-oxo-dA may modify transcriptional regulation under conditions of oxidative stress. In addition, the results obtained by Abraham and Brooks suggest that oligonucleotides encompassing an 8-oxo-dA -modified, NF-kappa B binding site might be useful therapeutic reagents for reducing the aberrant NF-kappa B-mediated signaling associated with several different diseases. Environ. Mol. Mutagen. 52:287-295, 2011 Published 2010 Wiley-Liss, Inc.