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Nucleic Acids Research Advance Access originally published online on September 23, 2008
Nucleic Acids Research 2008 36(18):6004-6012; doi:10.1093/nar/gkn595
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Nucleic Acids Research, 2008, Vol. 36, No. 18 6004-6012
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nucleic Acid Enzymes

Serial analysis of mutation spectra (SAMS): a new approach for the determination of mutation spectra of site-specific DNA damage and their sequence dependence

Huafeng Fang and John-Stephen Taylor*

Department of Chemistry, Washington University, St Louis, MO, USA

*To whom correspondence should be addressed. Tel: +1 314 935 6721; Fax: +1 314 935 4481; Email: taylor{at}wustl.edu

Received July 25, 2008. Revised September 2, 2008. Accepted September 3, 2008.

Many mutations occur as a result of DNA synthesis past the site of DNA damage by DNA damage bypass polymerases. The frequency and types of mutations not only depend on the nature of the damage, but also on the sequence context, as revealed from analysis of mutation spectra of DNA exposed to mutagens. Herein we report a new method for the rapid determination of the effect of sequence context on mutagenesis called SAMS for serial analysis of mutation spectra. This technique makes use of the methodology that underlies serial analysis of gene expression (SAGE) to analyze mutations that result from DNA synthesis past a DNA lesion site-specifically embedded in a library of DNA sequences. To illustrate our technique we determined the effect of sequence context on mutations generated by DNA synthesis past a tetrahydrofuran abasic site model by the DNA damage bypass polymerase yeast polymerase {eta}.


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