Repeat expansion by homologous recombination in the mouse germ line at palindromic sequences

Genetic instability can be induced by unusual DNA structures and sequence r epeats. We have previously demonstrated that a large palindrome in the mous e germ line derived from transgene integration is extremely unstable and un dergoes stabilizing rearrangements at high frequency, often through deletio ns that produce asymmetry. We have now characterized other palindrome rearr angements that arise from complex homologous recombination events. The stru cture of the recombinants is consistent with homologous recombination occur ring by a noncrossover gene conversion mechanism in which a break induced i n the palindrome promotes homologous strand invasion and repair synthesis, similar to mitotic break repair events reported in mammalian cells. Some of the homologous recombination events led to expansion in the size of the pa lindromic locus, which in the extreme case more than doubled the number of repeats. These results may have implications for instability observed at na turally occurring palindromic or quasipalindromic sequences.