Understanding BRCA1(-complexes) in DNA repair and cancer

Abstract

During my PhD, I dove into the world of genomic stability and DNA repair, important mechanisms in our body that protect us against cancer and many other diseases. The main focus of my PhD was BRCA1, a key protein in the DSB repair pathway HR, important for genomic stability. To complicate matters, BRCA1 is not only involved in HR, but also protects the replication fork during replication stress and suppresses ssDNA gap formation. Furthermore, BRCA1 is a large protein that forms different complexes with multiple different proteins. The specific BRCA1-complex formed in turn also influences the specific role BRCA1 can play in the cell. With this thesis, I aim to improve our understanding of the labyrinthine BRCA1 biology as well as highlight current gaps and contradictions within the field.