The DNA topoisomerase IIβ binding protein 1 (TopBP1) interacts with poly (ADP-ribose) polymerase (PARP-1)

We investigated the physical association of the DNA topoisomerase IIβ binding protein 1 (TopBP1), involved in DNA replication and repair but also in regulation of apoptosis, with poly(ADP‐ribose) polymerase‐1 (PARP‐1). This enzyme plays a crucial role in DNA repair and interacts with many DNA replication/repair factors. It was shown that the sixth BRCA1 C‐terminal (BRCT) domain of TopBP1 interacts with a protein fragment of PARP‐1 in vitro containing the DNA‐binding and the automodification domains. More significantly, the in vivo interaction of endogenous TopBP1 and PARP‐1 proteins could be shown in HeLa‐S3 cells by co‐immunoprecipitation. TopBP1 and PARP‐1 are localized within overlapping regions in the nucleus of HeLa‐S3 cells as shown by immunofluorescence. Exposure to UVB light slightly enhanced the interaction between both proteins. Furthermore, TopBP1 was detected in nuclear regions where poly(ADP‐ribose) (PAR) synthesis takes place and is ADP‐ribosylated by PARP‐1. Finally, cellular (ADP‐ribosyl)ating activity impairs binding of TopBP1 to Myc‐interacting zinc finger protein‐1 (Miz‐1). The results indicate an influence of post‐translational modifications of TopBP1 on its function during DNA repair. J. Cell. Biochem. 102: 171–182, 2007. © 2007 Wiley‐Liss, Inc.