Structural and thermo-mechanical analysis of BRCA1 BRCT variants in the cohort of patients in the Mi

BRCA1 is a key tumor suppressor gene that maintains the integrity of the genome through its C-terminal BRCTT double helix domain, by interfering with lipoprotein interactions in DNA damage response signaling pathways to disrupt protein stability and lipoprotein recognition. Variations in the BRCTT domain may affect protein stability and lipoprotein recognition; however, due to limited computer prediction and experimental evidence, its functional interpretation often conflicts. We characterized two Middle Eastern BRCA1BRCT variants, M1652I and F1662S, which were identified and compared in queues in Bahrain and Lebanon respectively.

We compared their structural and functional properties with the pathogenic R1699W variants. We assessed the structural stability, thermal stability of wild and mutant BRCA1 BRCT zones, as well as the semi-thermal instability and low focal temperature of BACH1 and CtIP tanks with hydrogen peroxide. The M1652I and F1662S retain a secondary structure and thermal stability in the region that is similar to that of the wild BRCA1; however, the R1699W exhibits a degree of semi-thermal instability and a lower focal point temperature that is different from that of the wild BRCA1.