NBS1 Activators

NBS1 Activators encompass a collection of chemical entities that indirectly enhance the functional activity of NBS1 within the cellular DNA damage response and repair systems. KU-55933 and AZD0156 act as ATM kinase inhibitors, which, by hindering the kinase's activity, inadvertently prompt a greater reliance on homologous recombination for DNA repair, a process in which NBS1 plays a pivotal role. Mirin and ETP-46464 similarly affect the MRN complex by inhibiting its exonuclease activity, thereby preventing the processing of DNA ends and enhancing the activation of NBS1 in checkpoint signaling and DNA repair. Chloroquine, through its inhibition of autophagy, indirectly stabilizes NBS1 by reducing its degradation, ensuring its availability for DNA damage signaling. NU7026, a DNA-PKcs inhibitor, and VE-821, an ATR inhibitor, both augment NBS1 function by increasing the cellular dependency on HR for the resolution of DNA damage, where NBS1's role is crucial.

Olaparib, Talazoparib, and Niraparib, all PARP inhibitors, enhance NBS1 activity by increasing the occurrence of DNA double-strand breaks that require NBS1-mediated repair through HR. The inhibition of Wip1 phosphatase by specific inhibitors keeps the DNA damage response activated longer, indirectly supporting the enhancement of NBS1's role in that response. Through these varied mechanisms, each chemical activator indirectly facilitates the enhancement of NBS1's involvement in the intricate network of pathways that maintain genomic stability. Collectively, they underscore the importance of NBS1's functional capacity in the cellular response to DNA damage, and their effects converge to amplify the critical activities of NBS1 in DNA repair processes.