Members of the L1 transposon family (long interpersed repeat DNA or LINE family) of rats are 6.7 kb long, 5 kb of which is devoted to two protein encoding genes. A regulatory region is at the left end of the element, and a guanine-rich polypurine: polypyrimidine sequences is near the right end. The protein encoding sequences of mammalian L1 families are highly conserved, but the regulatory sequences are completely distinct. Therefore, these families have been independently amplified in various mammalian species. We discovered the existence of ancient L1 families and our studies of them and their modern counterparts shows that extensive amplification events provide very robust phylogenetic information. We previously showed that the rat L1 element regulatory region strongly stimulates the activity of a gene fused to it which was the first evidence that L1 DNA is not just some non-functional """"""""junk"""""""" DNA. Although the DNA of the regulatory region can form specific complexes with nuclear DNA-binding proteins, the L1 regulatory region is not a typical transcriptional activator sequence since it stimulates gene activity solely by a post transcriptional mechanism. We earlier showed that the L1 guanine-rich polypurine: polypyrimidine sequence destabilizes contiguous duplex DNA, adopts several non-B DNA structures in vitro, and that it competes with target site non-B structures for supercoil energy which in vivo might modulate the supercoil dependent properties of L1 elements and their target sites. We now find that the L1 polypurine:pyrimidine sequence decreases the replication of plasmids in both bacteria and mammalian cells and alters the apparent activity of certain eukaryotic promoters in vivo. In parallel studies we have shown that homoguanine stretches enhance the mutation and recombination rate of adjacent DNA sequences in vivo.

Project Start
Project End
Budget Start
Budget End
Support Year
30
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code