Journal
NATURE
Volume 459, Issue 7250, Pages 1150-1153Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature08033
Keywords
-
Categories
Funding
- National Institutes of Health [R01 GM038464]
Ask authors/readers for more resources
Highly activated transcription is associated with eukaryotic genome instability, resulting in increased rates of mitotic recombination and mutagenesis. The association between high transcription and genome stability is probably due to a variety of factors including an enhanced accumulation of DNA damage, transcription-associated supercoiling, collision between replication forks and the transcription machinery, and the persistence of RNA-DNA hybrids(1). In the case of transcription-associated mutagenesis, we previously showed that there is a direct proportionality between the level of transcription and themutation rate in the yeast Saccharomyces cerevisiae(2), and that the molecular nature of the mutations is affected by highly activated transcription(2,3). Here we show that the accumulation of apurinic/apyrimidinic sites is greatly enhanced in highly transcribed yeast DNA. We further demonstrate that most apurinic/apyrimidinic sites in highly transcribed DNA are derived from the removal of uracil, the presence of which is linked to direct incorporation of dUTP in place of dTTP. These results show an unexpected relationship between transcription and the fidelity of DNA synthesis, and raise intriguing cell biological issues with regard to nucleotide pool compartmentalization.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available