DNA topoisomerase II-binding protein 1 (TOPBP1)

DNA topoisomerase II-binding protein 1 (TOPBP1) is a critical scaffold protein containing multiple BRCT domains that is essential for maintaining genomic stability (UniProt Q92547). It plays a central role in the DNA damage response (DDR) by acting as the primary activator of the ATR (Ataxia telangiectasia and Rad3-related) kinase, which orchestrates the cellular response to replication stress and DNA double-strand breaks (NCBI Gene ID: 11073). Beyond its role in ATR activation, TOPBP1 is involved in DNA replication initiation, transcriptional regulation, and the coordination of various repair proteins at damaged chromatin sites (PubMed PMID: 28604631). In the context of oncology, TOPBP1 is frequently overexpressed in several malignancies, including breast, lung, and ovarian cancers, where it contributes to therapeutic resistance and tumor cell survival under high levels of replicative stress (PubMed PMID: 33009416). Because of its pivotal role in the DDR, TOPBP1 is being investigated as a therapeutic target; inhibiting its function or its interaction with ATR can sensitize cancer cells to DNA-damaging agents and PARP inhibitors (PubMed PMID: 24631444).

Other names

TopBP1DNA topoisomerase II-beta-binding protein 1TOP2BP1KIAA0259

Inhibition of ATR kinase activation and disruption of DNA damage response scaffolding