TopBP1 contains transcriptional regulatory domains and regulates gene pathways involved in breast cancer

Excerpt

TopBP1 is a nuclear protein with eight BRCT domains and is involved in many aspects of nucleic acid metabolism: it is involved in the initiation of DNA replication in the Xenopus in vitro replication system by assisting loading of polymerase onto the replication complex; it is a substrate for ATM/ATR and is essential for the ATR DNA damage signalling pathway, and is also probably involved in the actual DNA repair process; it acts as a transcriptional cofactor for E2F1 where it regulates the apoptotic function of this protein. In addition, the yeast homologues of TopBP1, Dbp11 (Saccharomyces cerevisiae) and Cut5 (Schizo-saccharomyces pombe), are also involved in replication and repair processes. TopBP1 also shares functions with BRCA1; both are involved in regulating an intact G₂/M checkpoint, they colocalise to sites of DNA damage, they share sequence homology (even outside the BRCT domains), they are substrates for ATM/ATR, and they can regulate expression of the c-myc gene. All of these properties of TopBP1 led to us investigating whether TopBP1 plays a role in breast cancer. …