Sequence-dependent effect of interruptions on microsatellite mutation rate in mismatch repair-deficient human cells.

摘要: Although microsatellite mutation rates generally increase with increasing length of the repeat tract, interruptions in a may stabilize it. We have performed direct analysis effect on rate and spectrum cultured mammalian cells. Two mononucleotide sequences (G(17) A(17)) dinucleotide [(CA)(17)] were compared interrupted repeats same size 8 units. MMR-deficient (MMR(-)) cells used for these studies to eliminate effects this repair process. Mutation determined by fluctuation containing sequence at 5' end an antibiotic-resistance gene; vector carrying was integrated genome In general, had lower than perfect ones size, but magnitude difference dependent upon interrupting base(s). Some that those similar half length. This suggests bases effectively divide microsatellites into smaller runs mutational characteristics different from corresponding full-length microsatellite. conclude decrease influence frameshift mutations. The base(s) determines rate.