Replication of simple DNA repeats Review Article

This chapter presents an overview of studies on the replication of simple DNA repeats conducted in our laboratory during the last seven years. The recent massive increase in available DNA sequences has led to the clear understanding that natural DNAs, particularly in eukaryotes, are extraordinarily enriched in dif ferent repeats (Schroth and Ho, 1995; Cox and Mirkin, 1997) . This leads to an obvious quest ion: what are the biological functions ( i f any) of these repeated elements? This problem is currently the subject of very intense studies in many laboratories all over the world. We came to this question after we realized that many repeated DNA sequences constitute a major obstacle to DNA polymerization in v i t ro (Dayn et . a l . , 1992; Samadashwily et . a l . , 1993; Samadashwily and Mirkin, 1994; Krasilnikov et . al . , 1997). Subsequently, we found that several such repeats attenuate DNA replication i n v i v o as wel l (Samadashwily et . al . , 1997; Krasi lnikova et. al . , 1998). Based on our data, we conclude that there are at least three mechanisms by which different repeats inhibit replication. We believe that this may reflect a potentially important role of repeated DNA as punctuation marks for major genetic processes in DNA texts. Repeat-caused replication attenuation might also contribute to the mechanisms of repeat length polymorphism seen in many human diseases.