Mechanism of K63-linked polyubiquitin recognition and cleavage by the BRCA1-A complex.

ARISC-RAP80 recognizes and cleaves K63-linked polyubiquitin chains through a unique three-subunit interface, enabling precise DNA damage response regulation.

• Why it matters: Understanding how deubiquitylases target specific ubiquitin chains is crucial for elucidating DNA repair mechanisms and cancer prevention pathways, yet the detailed recognition process remains unclear.
• What they did: The study used structure-guided mutagenesis and cell-based assays to analyze how ARISC-RAP80 interacts with K63-linked polyubiquitin chains, revealing key recognition interfaces.
• The result: Findings show that ARISC-RAP80’s recognition involves a composite interface that positions ubiquitin chains for cleavage, linking ubiquitin decoding to chromatin recruitment and DNA repair functions.