Exploiting DNA Ligase III addiction of multiple myeloma by flavonoid Rhamnetin.

ABSTRACT:

Background

DNA ligases are crucial for DNA repair and cell replication since they catalyze the final steps in which DNA breaks are joined. DNA Ligase III (LIG3) exerts a pivotal role in Alternative-Non-Homologous End Joining Repair (Alt-NHEJ), an error-prone DNA repair pathway often up-regulated in genomically unstable cancer, such as Multiple Myeloma (MM). Based on the three-dimensional (3D) LIG3 structure, we performed a computational screening to identify LIG3-targeting natural compounds as potential candidates to counteract Alt-NHEJ activity in MM.

Methods

Virtual screening was conducted by interrogating the Phenol Explorer database. Validation of binding to LIG3 recombinant protein was performed by Saturation Transfer Difference (STD)-nuclear magnetic resonance (NMR) ex

SUBMITTER: Caracciolo D 

PROVIDER: S-EPMC9588242 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature