INDUCTION OF LARGE DNA PALINDROME FORMATION IN YEAST - IMPLICATIONS FOR GENE AMPLIFICATION AND GENOME STABILITY IN EUKARYOTES

Many amplified genes, including some oncogenes, are organized as large inverted repeats. How such giant palindromes are generated remains la rgely unknown. Recent studies of a palindrome in the ciliate Tetrahyme na suggest a novel mechanism that requires chromosome breakage next to short inverted repeats. The prevalence of short inverted repeats in e ukaryotic genomes raises the interesting possibility that this process may occur widely as a response to chromosome damage. Here we demonstr ate that in Saccharomyces cerevisiae, large DNA palindromes are formed efficiently, probably by intramolecular recombination, when a double- strand break is introduced next to short inverted repeats. These resul ts suggest a general mechanism for large palindromic DNA formation and reveal an important new source of genome instability resulting from c hromosome breakage at selective sites.