germline mutations, breast cancer
A recent study by Lou et al. showed that knocking down either BRCA1 or topoisomerase IIα in HCC1937 cells (breast cancer cell line) and HeLa cells resulted in defective chromosome condensation and lagging chromosomes during mitosis. Thus, BRCA1 plays a role in DNA decatenation. Previously, Baer and Ludwig showed that the N-terminus of BRCA1 forms a heterodimer with BARD1, and together this complex acts as an active ubiquitin polymerase. Lou et al. found that topoisomerase IIα immunoprecipitated from cells that produced endogenous BRCA1 was ubiquitinated, while topoisomerase IIα from cells lacking BRCA1 was not ubiquitinated. Furthermore, ubiquitination of topoisomerase IIα lead to an increase in its activity. However, no evidence was shown for a direct role of BRCA1 in ubiquitinating topoisomerase IIα. Is BRCA1 directly interacting with topoisomerase IIα , ubiquitinating it through its N-terminus, or is it playing a role as an upstream regulator of topoisomerase IIα?
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