Transcriptional Processing of G4 DNA

Genomic DNA sequences with the ability to assume non-B form secondary structures have been recently shown to be particularly susceptible to genetic instability, an early contributing factor in human disease and cancer development. Transcription appears to play a central role in formation of these structures and in promoting instability at these sites. The subpathway of nucleotide excision DNA repair, transcription-coupled DNA repair (TCR), removes transcription-arresting damage from the transcribed strands of expressed genes, but little is known about how noncanonical DNA structures are processed when encountered by the transcription machinery. If such structures arrest transcription, they may elicit gratuitous TCR in which the resulting reiterative and futile repair replication might generate a significant level of mutagenesis in a frequently transcribed gene because of faulty processing in the area of transcription arrest. Here we will describe our current understanding of how TCR may be elicited at non-B DNA structures and summarize recent literature describing the behavior of RNA polymerases when encountering noncanonical DNA structures, with particular emphasis on quadruplex DNA. (C) 2009 Wiley-Liss, Inc.