Topoisomerases interlink genetic network underlying autism

• Topoisomerases are specific enzymes that solve topological problems arising from DNA supercoiling during processes such as replication, transcription, recombination, chromatin remodeling, chromosome condensation and segregation. Topoisomerases are involved in neural gene expression essential for cell differentiation, synapse formation, cell migration and axon guidance; processes important for CNS development.
• Topoisomerases induced expression of the same group of genes as those associated with autism.
• Defects in gene transcription, in terms of disrupted Top1 or Top2 activity, affecting long genes expressed in neurons, and in critical stages of brain development can be the underlying cause of pathology in many autistic individuals.

DNA topoisomerases belong to the group of proteins that play an important role in the organizational dynamics of the human genome. Their enzymatic activity solves topological strain rising from DNA supercoiling occurring during transcription. DNA topoisomerases are especially important for transcription of genes involved in neurodevelopment. Disruption of topoisomerase activity in animal models resulted in impaired neurodevelopment and changed brain architecture. Recent research revealed that topoisomerases induced expression of the same group of genes as those associated with autism. Transcriptional inhibition of neuronal genes during critical stages of brain development may be responsible for pathology of neurodevelopmental disorders such as autism. In this review we aim to outline the role of topoisomerase in neurodevelopment and its possible linkage to neuropathology of autism.