STABILITY OF MICROSATELLITES AND MINISATELLITES IN BLOOM-SYNDROME, A HUMAN SYNDROME OF GENETIC INSTABILITY

Bloom syndrome (BS) is a human cancer-prone genetic disorder essential ly characterized by a generalized genetic instability including a high level of sister chromatid exchanges (SCEs). Although mutator and hype r-Rec phenotypes of BS cells present analogies with those of bacteria and yeast defective in DNA mismatch repair, we report that (CA), micro satellite alterations are undetectable in BS cells. Thus, our results suggest that the origin of BS mutator phenotype is not a major defect in DNA mismatch repair, allowing us to eliminate an attractive hypothe sis for the pleiotropy of BS. We previously suggested that at least so me of the intra-allelic rearrangements occurring in minisatellites cou ld result from unequal SCEs. Although SCEs are abnormally frequent in BS cells, the present study failed to show any significant variation o f the mutation rates of the two hypermutable minisatellites we analyze d. Thus, our results show that, in spite of an overall genetic instabi lity, alterations in structural motifs known to be predisposed to inst ability by different mechanisms are undetectable in BS cells.