A 140-BP-LONG PALINDROMIC SEQUENCE INDUCES DOUBLE-STRAND BREAKS DURING MEIOSIS IN THE YEAST SACCHAROMYCES-CEREVISIAE

Palindromic sequences have the potential to form hairpin or cruciform structures, which are putative substrates for several nucleases and mi smatch repair enzymes. A genetic method was developed to detect such s tructures in vivo in the yeast Saccharomyces cerevisiae. Using this me thod we previously showed that short hairpin structures are poorly rep aired by the mismatch repair system in S. cerevisiae. We show here tha t mismatches, when present in the stem of the hairpin structure, are n ot processed by the repair machinery, suggesting that they are treated differently than those in the interstrand base-paired duplex DNA. A 1 40-bp-long palindromic sequence, on the contrary, acts as a meiotic re combination hotspot by generating a site for a double-strand break, an initiator of meiotic recombination. We suggest that long palindromic sequences undergo cruciform extrusion more readily than short ones. Th is cruciform structure then acts as a substrate for structure-specific nucleases resulting in the formation of a double-strand break during meiosis in yeast. In addition, we show that residual repair of the sho rt hairpin structure occurs in an MSH2-independent pathway.