BRCA1 Mutational Complementation Induces Synthetic Viability.

ABSTRACT: BRCA1 promotes the DNA end resection and RAD51 loading steps of homologous recombination (HR). Whether these functions can be uncoupled, and whether mutant proteins retaining partial activity can complement one another, is unclear and could affect the severity of BRCA1-associated Fanconi anemia (FA). Here we generated a Brca1^CC mouse with a coiled-coil (CC) domain deletion. Brca1^CC/CC mice are born at low frequencies, and post-natal mice have FA-like abnormalities, including bone marrow failure. Intercrossing with Brca1^Δ11, which is homozygous lethal, generated Brca1^CC/Δ11 mice at Mendelian frequencies that were indistinguishable from Brca1^+/+ mice. Brca1^CC and Brca1^Δ11 proteins were individually responsible for c

SUBMITTER: Nacson J 

PROVIDER: S-EPMC7418109 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature