| First Author | Mamouni K | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 16 | Pages | 3144-55 |
| PubMed ID | 24912678 | Mgi Jnum | J:224276 |
| Mgi Id | MGI:5661806 | Doi | 10.1128/MCB.01525-13 |
| Citation | Mamouni K, et al. (2014) RhoB promotes gammaH2AX dephosphorylation and DNA double-strand break repair. Mol Cell Biol 34(16):3144-55 |
| abstractText | Unlike other Rho GTPases, RhoB is rapidly induced by DNA damage, and its expression level decreases during cancer progression. Because inefficient repair of DNA double-strand breaks (DSBs) can lead to cancer, we investigated whether camptothecin, an anticancer drug that produces DSBs, induces RhoB expression and examined its role in the camptothecin-induced DNA damage response. We show that in camptothecin-treated cells, DSBs induce RhoB expression by a mechanism that depends notably on Chk2 and its substrate HuR, which binds to RhoB mRNA and protects it against degradation. RhoB-deficient cells fail to dephosphorylate gammaH2AX following camptothecin removal and show reduced efficiency of DSB repair by homologous recombination. These cells also show decreased activity of protein phosphatase 2A (PP2A), a phosphatase for gammaH2AX and other DNA damage and repair proteins. Thus, we propose that DSBs activate a Chk2-HuR-RhoB pathway that promotes PP2A-mediated dephosphorylation of gammaH2AX and DSB repair. Finally, we show that RhoB-deficient cells accumulate endogenous gammaH2AX and chromosomal abnormalities, suggesting that RhoB loss increases DSB-mediated genomic instability and tumor progression. |
