The impact of imbalance in alkyladenine DNA glycosylase on mouse brain development, cognition, behaviour and response to ischemic injury

Base excision repair (BER) is the major pathway for the removal of damaged DNA bases. DNA base damage is generated upon exposure to damaging agents present in our environment, food, water and inside cells as natural metabolites. The accumulation of DNA damage is considered to contribute to the onset of neurodevelopmental disorders, cancer and to promote ageing. The specificity of BER is determined by DNA glycosylases that recognize damaged bases and initiate the pathway. Alkyladenine DNA glycosylase (AAG) is the main glycosylase that removes alkylated DNA bases. Recent findings identified that loss of DNA glycosylases responsible for repair of oxidised bases results in impaired brain development, cognition, behaviour and response to ischemic injury. Currently it is unknown how AAG dysbalance affects these processes. By using AAG-deficient and -transgenic mouse models we would like to elucidate the role of AAG in neurodevelopment, behaviour, cognition and response to brain injury.