Mechanism for survival of homozygous nonsense mutations in the tumor suppressor gene BRCA1

• DOI: 10.1073/pnas.1801796115
• Publication Date: 2018-04-30T19:17:40Z
• Authors: Aaron Seo; Orna Steinberg-Sh...; Sule Unal; Silvia Casadei; Tom Walsh; Fatma Gumruk; Stavit Shalev; Akiko Shimamura; Nurten Ayse Akarsu; Hannah Tamary; Mary-Claire King
• Keywords: Nonsense mutation; Nonsense; Loss function

Significance Many patients with breast and ovarian cancer carry inherited cancer-predisposing mutations in BRCA1 . However, virtually no have two because the DNA repair function of is essential for embryonic development. We discovered that nonsense from a specific region may survive as result naturally occurring alternative splicing yields short but partially functional protein. These are extremely rare, characterized by severe chromosomal fragility, congenital anomalies, predisposition to childhood cancers.