Meiotic recombination in the yeast Saccharomyces cerevisiae is initiated by programmed double-strand breaks at selected sites throughout the genome (hotspots). alpha-Hotspots are binding sites for transcription factors. Double-strand breaks at alpha-hotspots require binding of transcription factor but not high levels of transcription per se. We show that modulating the production of the transcription factor Gcn4p by deletion or constitutive transcription alters the rate of gene conversion and crossing-over at HIS4. In addition, we show that alterations in the metabolic state of the cell change the frequency of gene conversion at HIS4 in a Gcn4p-dependent manner. We suggest that recombination data obtained from experiments using amino acid and other biosynthetic genes for gene disruptions and/or as genetic markers should be treated cautiously. The demonstration that Gcn4p affects transcription of more than 500 genes and that the recombinationally "hottest" ORFs tend to be Gcn4p-regulated suggest that the metabolic state of a cell, especially with respect to nitrogen metabolism, is a determinant of recombination rates. This observation suggests that the effects of metabolic state may be global and may account for some as yet unexplained features of recombination in higher organisms, such as the differences in map length between the sexes.
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