Ontology highlight
ABSTRACT:
SUBMITTER: Tan SLW
PROVIDER: S-EPMC5457488 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Tan Shawn Lu Wen SLW Chadha Saakshi S Liu Yansheng Y Gabasova Evelina E Perera David D Ahmed Karim K Constantinou Stephanie S Renaudin Xavier X Lee MiYoung M Aebersold Ruedi R Venkitaraman Ashok R AR
Cell 20170601 6
Mutations truncating a single copy of the tumor suppressor, BRCA2, cause cancer susceptibility. In cells bearing such heterozygous mutations, we find that a cellular metabolite and ubiquitous environmental toxin, formaldehyde, stalls and destabilizes DNA replication forks, engendering structural chromosomal aberrations. Formaldehyde selectively depletes BRCA2 via proteasomal degradation, a mechanism of toxicity that affects very few additional cellular proteins. Heterozygous BRCA2 truncations, b ...[more]