Proline variants in the BRCA1 coiled-coil domain disrupt folding and binding to PALB2.

ABSTRACT: Inherited mutations in the genes coding for the tumor suppressor proteins BRCA1 and PALB2 can lead to increased risk of breast and ovarian cancer. Upon DNA damage, these two proteins form a complex to promote double-stranded break repair via homologous recombination. Missense mutations in either BRCA1 or PALB2 that disrupt this important interaction result in loss of effective DNA damage repair and are associated with breast tumorigenesis. However, the overwhelming majority of missense mutations found in the binding domains of these two genes remain classified as variants of unknown significance. Here we report an in vitro assay for assessing the effect of variants of unknown significance on the heterodimerization of PALB2 and BRCA1 that recapitulates the effect of the known deleterious mu

SUBMITTER: Baker CNS 

PROVIDER: S-EPMC11645666 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature