Objectives: Through multi-disciplinary approaches identify the role of canonical repair DNA glycosylases in genome regulation. The prevailing view in the field was that a major role of DNA glycosylases is to repair aberrant DNA bases and thus prevent the fixation of mutations. However, to which extent loss of DNA glycosylases causes cancer and how glycosylases operate on chromatin was not enterally understood.

Outcomes: This project resulted in milestone publications in the field, demonstrating that: (I) loss of different DNA glycosylases do not cause increased cancer incidence); instead (II) DNA glycosylases associate with active transcription and regulate gene expression, primarily of neurodevelopmental genes, and (III) influence spectra of epigenetic modifications and (IV) ribonucleotide levels in the genome. Further, the project provided directions for analysis of transcriptional responses in cancer cells and their importance for repurposing treatment with alkylating drugs. Besides these findings, the projects yielded a battery of biochemical and cell tools to study functions of DNA glycosylases.