Supervisori: Prof. Tell e Prof.ssa Antoniali

The role of APE1 in cancer resistance: APE1 Condensates in DNA Damage Repair and miRNA processing

Apurinic/apyrimidinic Endodeoxyribonuclease 1 (APE1) is a multifunctional protein involved DNA damage repair, transcription and RNA metabolism. RNA binding proteins are known to interact with APE1 but the functional role of these interactions is mostly unknown. APE1 is often overexpressed in many cancers but its role in tumor progression and chemoresistance has been not fully elucidated, yet. Phase separation is emerging as a novel mechanism to concentrate DNA repair enzymes at the lesion sites, among different characteristics, Internal Disordered Regions of proteins can promote phase separation, which has been involved in drug resistance of some cancers.
This project aims to investigate whether APE1 activity occurs within condensates, focusing on its DNA damage repair and miRNA processing functions. Small molecules can partition into specific condensates, this project could be the stepping stone for designing novel APE1 inhibitors to better target its altered activity in cancer cells.