L1 retrotransposable elements are high copy number genomic parasites found in mammals and are thought to cause as many as 0.2% of the genetic defects in humans. L1 elements are 6-7 kb long and contain two protein encoding genes. A regulatory region is at the left end of the element, and a guanine-rich polypurine:polypyrimidine sequence is near the right end. The protein encoding sequences of mammalian L1 families are highly conserved, but the regulatory sequences are completely distinct. We discovered the existence of ancient L1 families in mammalian genome and our studies of them and their modern counterparts showed that extensive amplification of L1 elements has been episodic and recurrent during mammalian evolution, and that L1 amplification events provide very robust phylogenetic information. We previously showed that the regulatory region of the rat L1 element 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 by acting as an activator of protein translation. Dr. Usdin has extended her work on non-B (abnormal) DNA structures. Her group has shown that an unusual nucleic acid structure is a highly conserved feature of the 3' untranslated region of L1 elements which strongly indicates that is vital for the biological activity of L1 elements. She also has discovered a new class of very strong DNA synthesis arrest sites that is abundant in the genome of man organisms. The molecular basis of the arrest is the formation of a K+ dependent intrastrand tetrahelical structure. She speculates that the arrest of DNA synthesis or other possible effects of the tetrahelical structure could account for the genetic instability that is associated with these sequence motifs.
