Recombinogenic Effects of DNA-Damaging Agents Are Synergistically Increased by Transcription in Saccharomyces cerevisiae: New Insights Into Transcription-Associated Recombination

Corresponding author: A. Aguilera, Facultad de Biología, Universidad de Sevilla, Avd. Reina Mercedes 6, 41012 Sevilla, Spain., aguilo{at}us.es (E-mail)

Communicating editor: S. LOVETT

Homologous recombination of a particular DNA sequence is strongly stimulated by transcription, a phenomenon observed from bacteria to mammals , which we refer to as transcription-associated recombination (TAR). TAR might be an accidental feature of DNA chemistry with important consequences for genetic stability. However, it is also essential for developmentally regulated processes such as class switching of immunoglobulin genes. Consequently, it is likely that TAR embraces more than one mechanism. In this study we tested the possibility that transcription induces recombination by making DNA more susceptible to recombinogenic DNA damage. Using different plasmid-chromosome and direct-repeat recombination constructs in which transcription is driven from either the P_GAL1- or the P_tet-regulated promoters, we have shown that either 4-nitroquinoline-N-oxide (4-NQO) or methyl methanesulfonate (MMS) produces a synergistic increase of recombination when combined with transcription. 4-NQO and MMS stimulated recombination of a transcriptionally active DNA sequence up to 12,800- and 130-fold above the spontaneous levels observed in the absence of transcription, whereas 4-NQO and MMS alone increased recombination 193- and 4.5-fold, respectively. Our results provide evidence that TAR is due, at least in part, to the ability of transcription to enhance the accessibility of DNA to exogenous chemicals and internal metabolites responsible for recombinogenic lesions. We discuss possible parallelisms between the mechanisms of induction of recombination and mutation by transcription.

This article has been cited by other articles:

				B. C. Del Rosario and L. F. Pemberton Nap1 Links Transcription Elongation, Chromatin Assembly, and Messenger RNP Complex Biogenesis Mol. Cell. Biol., April 1, 2008; 28(7): 2113 - 2124. [Abstract] [Full Text] [PDF]

				B. Gomez-Gonzalez and A. Aguilera Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex PNAS, May 15, 2007; 104(20): 8409 - 8414. [Abstract] [Full Text] [PDF]

				P. Huertas, M. L. Garcia-Rubio, R. E. Wellinger, R. Luna, and A. Aguilera An hpr1 Point Mutation That Impairs Transcription and mRNP Biogenesis without Increasing Recombination Mol. Cell. Biol., October 15, 2006; 26(20): 7451 - 7465. [Abstract] [Full Text] [PDF]

				X. Li and J. L. Manley Cotranscriptional processes and their influence on genome stability Genes & Dev., July 15, 2006; 20(14): 1838 - 1847. [Abstract] [Full Text] [PDF]

				J. Loidl and H. Scherthan Organization and pairing of meiotic chromosomes in the ciliate Tetrahymena thermophila J. Cell Sci., November 15, 2004; 117(24): 5791 - 5801. [Abstract] [Full Text] [PDF]

				M. J. Lippert, J. A. Freedman, M. A. Barber, and S. Jinks-Robertson Identification of a Distinctive Mutation Spectrum Associated with High Levels of Transcription in Yeast Mol. Cell. Biol., June 1, 2004; 24(11): 4801 - 4809. [Abstract] [Full Text] [PDF]