Polar alteration of short tandem repeats (STRs) in mammalian cells

Instability of short tandem repeats (STRs) in DNA during replication is obs erved in all organisms examined. and is causatively involved in various hum an diseases. We explore the mechanisms involved in instability by examining length changes occurring during the replication of [(CA)(20),TA](n) and [( CAG)(20)TAG](n), in human cells. We show that the majority of alterations c onsist of an insertion or deletion of one repeat unit, and base substitutio ns or length changes involving many repeat units are rare. We also show tha t length changes of two-tract STRs are biased toward the 3'-end of the repe at tract, in reference to lagging strand synthesis. There are some differen ces between our observations and previous observations in microbes, e.g. th e orientation effect was not observed in this study. The results of this st udy are discussed in terms of the molecular mechanisms leading to alteratio ns in repeat tracts. (C) 2001 Elsevier Science B.V. All rights reserved.