DNA Conformation Dynamics and Human Diseases

Boian S. Alexandrov, T-1; Alan R. Bishop, PADSTE; Luba Kalaydjieva, Western Australian Institute for Medical Research; I. S. Kohane, Childrens Hospital, Harvard Medical School; Kim Ø. Rasmussen, T-5; Anny Usheva, Beth Israel Deaconess Medical Center; V. I. Valtchinov, Harvard Medical School The inherent thermal motion that a DNA molecule is subjected to in a living cell makes it possible for the two strands of the molecule to locally and spontaneously open and close. This dynamic effect is referred to as “DNA breathing” because it induces local transient separation of complementary base pairs. Numerous prior studies that combine modeling and experiments have firmly established a connection between this localized breathing dynamic of DNA and functional characteristics of mammalian transcriptional promoters. Here we highlight two recent studies that utilized the relationship between the breathing dynamics of DNA and biological function to elucidate some of the mechanisms of pathogenesis and progression in cognitive deficit schizophrenia, Friedreich’s ataxia, Huntington’s disease, and Fragile X-syndrome.