Identification and functional analysis of TopBP1 and its homologs

The multiple BRCT-domain protein TopBP1 and its yeast homologs have been implicated in many aspects of DNA metabolism, but their molecular functions remain elusive. In this review, we first summarise how the yeast homologs were identified and characterised. We next review the data available from metazoan systems and finally draw parallels with the yeast models. TopBP1 plays important functions in the initiation of DNA replication in all organisms and participates in checkpoint responses both within S phase and following DNA damage. In metazoan systems there is accumulating evidence for additional roles in transcriptional regulation that have not been reported in yeast. Overall, TopBP1 appears to play a key role in integrating different aspects of DNA metabolism, but the mechanistic basis for this remains to be fully explained.