Mechanisms of BRCA1-BARD1 nucleosome recognition and ubiquitylation.

ABSTRACT: The BRCA1-BARD1 tumour suppressor is an E3 ubiquitin ligase necessary for the repair of DNA double-strand breaks by homologous recombination^1-10. The BRCA1-BARD1 complex localizes to damaged chromatin after DNA replication and catalyses the ubiquitylation of histone H2A and other cellular targets^11-14. The molecular bases for the recruitment to double-strand breaks and target recognition of BRCA1-BARD1 remain unknown. Here we use cryo-electron microscopy to show that the ankyrin repeat and tandem BRCT domains in BARD1 adopt a compact fold and bind to nucleosomal histones, DNA and monoubiquitin attached to H2A amino-terminal K13 or K15, two signals known to be specific for double-strand breaks^15,16. We further show that RING domains¹⁷ in BRCA1-BAR

SUBMITTER: Hu Q 

PROVIDER: S-EPMC8680157 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature