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 <i>Cancer Research</i>, 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 (<i>Brca1^LP</i> ), which disrupts its binding with PALB2. Unlike the previously reported viable coiled-coil defective mice, homozygous <i>Brca1^LP/LP</i> 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 <i>Brca1</i> and <i>Trp53</i> in mice. The findings reveal the relevance of the coiled-coil domain in mammary tumor suppression by BRCA1.<i>See related article by Pulver et al., p. 6171</i>.