Microsatellite instability in Drosophila spellchecker1 (MutS homolog) mutants

We have cloned a mutS homolog from Drosophila melanogaster called spellchec ker1 (spel1) and have constructed spell mutant Plies, MutS proteins promote the correction of DNA mismatches and serve important roles in DNA replicat ion, recombination, and repair. The spell gene belongs to a subfamily of mu tS first characterized pv the MSH2 gene of yeast and which also includes hM SH2, one of the two major hereditary nonpolyposis colon cancer loci of huma ns. Like msh2 mutants in other species, we find that flies lacking the spel l gene suffer a highly increased rate of instability in long runs of dinucl eotide repeats when analyzed after 10-12 fly generations. Using a new assay we have also discovered that mutations in spell decrease the stability of a dinucleotide repeat when it is copied into the site of a double-strand br eak during gene conversion. Contrary to the case in mammalian cells, spell deficiency does not affect tolerance of flies to a methylating agent nor do es it affect resistance to gamma-irradiation.