TopBP1: A BRCT-scaffold protein functioning in multiple cellular pathways

Human TopBP1 contains nine BRCT domains and functions in DNA replication initiation, checkpoint signalling, DNA repair and influences transcriptional control. TopBP1 and its homologues have been the subject of numerous scientific publications since the last comprehensive review in 2005, emerging as a key scaffold protein that links crucial components within these distinct cellular processes. This review focuses on recently published work, with particular emphasis on structural insights into TopBP1 function and the binding partners identified for DNA replication initiation, DNA-dependent checkpoints, DNA repair and transcription. We further summarise what is known about TopBP1 and links to human disease.