Dipeptidyl peptidase 9 triggers BRCA2 degradation and promotes DNA-damage repair

ABSTRACT: N-terminal sequences are important sites for post-translational modifications that alter protein localization, activity and stability. Dipeptidyl peptidase 9 (DPP9) is a serine aminopeptidase with the rare ability to cleave off N-terminal dipeptides with imino-acid proline in the second position. Here, we identify the tumour-suppressor BRCA2 as a DPP9 substrate and show this interaction to be induced by DNA damage. We present crystallographic structures documenting intra-crystalline enzymatic activity of DPP9, with the N-terminal Met1-Pro2 of a BRCA21-40 peptide captured in its active-site. Intriguingly, DPP9-depleted cells are hypersensitive to genotoxic agents and are impaired in repair of DNA double-strand breaks by Homologous-Recombination. Mechanistically, DPP9 targets BRCA2 for degra

SUBMITTER: Oguz Bolgi 

PROVIDER: S-SCDT-EMBOR-2021-54136V1 | biostudies-other |

REPOSITORIES: biostudies-other