Childhood Neurodegenerative Diseases Linked to Common DNA Repair Problem

In a recent study published in the journal Nature Neuroscience, researchers at St. Jude Children’s Research Hospital linked two rare, inherited childhood neurodegenerative diseases to a new source of DNA damage that may play a role in a wide range of health problems, including cancer. During the study, researchers found that an enzyme required for normal DNA functioning causes DNA damage in the developing brain. The enzyme, topoisomerase 1 (Top1), works by temporarily attaching to and forming a short-lived molecule called a Top1 cleavage complex (Top1cc). Top1ccs cause reversible breaks in one strange of the double-stranded DNA molecule. Different factors, including the free radicals that are a byproduct of oxygen metabolism, result in Top1ccs becoming trapped on DNA and accumulating in cells. This study is the first to link the buildup to disease and the results broaden the scientific understanding of the mechanisms that maintain brain health. Researchers made the connection between DNA damage and accumulation of Top1ccs while studying DNA repair problems in the rare neurodegenerative disorders ataxia telangiectasia (A-T) and spinocerebellar ataxia with axonal neuropathy 1(SCAN1). The diseases both involve progressive difficulty with walking and other movement. To read more about this study, click here.