BCAT1 Associates with DNA Repair Proteins KU70 and KU80 and Contributes to Regulate DNA Repair in T-Cell Acute Lymphoblastic Leukemia (T-ALL).

ABSTRACT: Increased expression of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) often correlates with tumor aggressiveness and drug resistance in cancer. We have recently reported that BCAT1 was overexpressed in a subgroup of T-cell acute lymphoblastic (T-ALL) samples, especially those with NOTCH1 activating mutations. Interestingly, BCAT1-depleted cells showed pronounced sensitivity to DNA-damaging agents such as etoposide; however, how BCAT1 regulates this sensitivity remains uncertain. Here, we provide further clues on its chemo-sensitizing effect. Indeed, BCAT1 protein regulates the non-homologous end joining (c-NHEJ) DNA repair pathway by physically associating with the KU70/KU80 heterodimer. BCAT1 inhibition during active repair of DNA double-strand breaks (DSBs) led to increased KU7

SUBMITTER: Tosello V 

PROVIDER: S-EPMC11676169 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature