TRANSCRIPTION FACTOR MTS1 MTS2 (ATF1/PCR1, GAD7/PCR1) ACTIVATES THE M26 MEIOTIC RECOMBINATION HOTSPOT IN SCHIZOSACCHAROMYCES-POMBE/

Homologous recombination hotspots increase the frequency of recombinat ion in nearby DNA. The M26 hotspot in the ade6 gene of Schizosaccharom yces pombe is a meiotic hotspot with a discrete, cis-acting nucleotide sequence (5'-ATGACGT-3') defined by extensive mutagenesis. A heterodi meric M26 DNA binding protein, composed of subunits Mts1 and Mts2, has been identified and purified 40,000-fold. Cloning, disruption, and ge netic analyses of the mts genes demonstrate that the Mts1/Mts2 heterod imer is essential for hotspot activity. This provides direct evidence that a specific trans-acting factor, binding to a cis-acting site with a unique nucleotide sequence, is required to activate this meiotic ho tspot. Intriguingly, the Mts1/Mts2 protein subunits are identical to t he recently described transcription factors Atf1 (Gad7) and Pcr1, whic h are required for a variety of stress responses. However, we report d ifferential dependence on the Mts proteins for hotspot activation and stress response, suggesting that these proteins are multifunctional an d have distinct activities. Furthermore, ade6 mRNA levels are equivale nt in hotspot and nonhotspot meioses and do not change in mts mutants, indicating that hotspot activation is not a consequence of elevated t ranscription levels. These findings suggest an intimate but separable link between the regulation of transcription and meiotic recombination . Other studies have recently shown that the Mts1/Mts2 protein and M26 sites are involved in meiotic recombination elsewhere in the S. pombe genome, suggesting that these factors help regulate the timing and di stribution of homologous recombination.