Expansion of the CCG trinucleotide repeats give rise to the folate-sensitive group of fragile sites. Expansion of AGC repeats give rise to a number of neurological disorders, including myotonic dystrophy and Huntington disease. Recent work implies that the process of dynamic mutation is relevant to repeats of various composition and length such as the H-ras VNTR and the VNTR in the diabetes susceptibility locus involved in insulin transcription. Thus, dynamic mutation is very important to a host of human diseases. We have been able to find conditions that generate dramatic repeat expansion in vitro and we are actively investigating the mechanisms involved.
Additional work is underway to probe the role of repeat expansion in cancer.
Changing a leucine to a lysine residue makes Nael endonuclease hypersensitive to DNA intercalative drugs. A model for restriction endonuclease evolution. Nucleic Acids Res .