Saltar al contenido
MilliporeSigma

hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors.

Cellular signalling (2021-08-08)
Ramazan Gundogdu, M Kadir Erdogan, Angeliki Ditsiou, Victoria Spanswick, Juan Jose Garcia-Gomez, John A Hartley, Fumiko Esashi, Alexander Hergovich, Valenti Gomez
RESUMEN

Monopolar spindle-one binder (MOBs) proteins are evolutionarily conserved and contribute to various cellular signalling pathways. Recently, we reported that hMOB2 functions in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest in untransformed cells. However, the question of how hMOB2 protects cells from endogenous DNA damage accumulation remained enigmatic. Here, we uncover hMOB2 as a regulator of double-strand break (DSB) repair by homologous recombination (HR). hMOB2 supports the phosphorylation and accumulation of the RAD51 recombinase on resected single-strand DNA (ssDNA) overhangs. Physiologically, hMOB2 expression supports cancer cell survival in response to DSB-inducing anti-cancer compounds. Specifically, loss of hMOB2 renders ovarian and other cancer cells more vulnerable to FDA-approved PARP inhibitors. Reduced MOB2 expression correlates with increased overall survival in patients suffering from ovarian carcinoma. Taken together, our findings suggest that hMOB2 expression may serve as a candidate stratification biomarker of patients for HR-deficiency targeted cancer therapies, such as PARP inhibitor treatments.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Anti-BRCA2 (Ab-1) Mouse mAb (2B), liquid, clone 2B, Calbiochem®
Sigma-Aldrich
Anti-ATM Antibody, Upstate®, from rabbit
Sigma-Aldrich
Anti-Replication Protein A (Ab-1) Mouse mAb (RPA70-9), liquid, clone RPA70-9, Calbiochem®