Coiled-Coil Domain: Uncoiling Tumor Suppression by BRCA1.

Abstract

The coiled-coil domain of BRCA1 is essential for its interaction with partner and localizer of BRCA2 (PALB2). In mice, loss of this interaction is known to result in Fanconi anemia-associated phenotypes. In a study published in this issue of Cancer Research, Pulver and colleagues from the Jonkers lab have generated a mouse model with a leucine to proline change in codon 1363 in the coiled-coil domain of BRCA1 (Brca1LP ), which disrupts its binding with PALB2. Unlike the previously reported viable coiled-coil defective mice, homozygous Brca1LP/LP mutant mice die during embryogenesis. The authors examined the role of the BRCA1/PALB2 interaction on mammary tumorigenesis and reported increased incidence of mammary tumors that are carcinosarcomas or sarcomatoids, unlike the adenocarcinomas that are characteristic mammary tumor types associated with loss of Brca1 and Trp53 in mice. The findings reveal the relevance of the coiled-coil domain in mammary tumor suppression by BRCA1.See related article by Pulver et al., p. 6171.