RhoB promotes γH2AX dephosphorylation and DNA double-strand break repair

Kenza Mamouni, Agnese Cristini, Josée Guirouilh-Barbat, Sylvie Monferran, Anthony Lemarié, Jean Charles Faye, Bernard S. Lopez, Gilles Favre, Olivier Sordet

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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 γH2AX 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 γH2AX and other DNA damage and repair proteins. Thus, we propose that DSBs activate a Chk2-HuR-RhoB pathway that promotes PP2A-mediated dephosphorylation of γH2AX and DSB repair. Finally, we show that RhoB-deficient cells accumulate endogenous γH2AX and chromosomal abnormalities, suggesting that RhoB loss increases DSB-mediated genomic instability and tumor progression.

Original languageEnglish (US)
Pages (from-to)3144-3155
Number of pages12
JournalMolecular and Cellular Biology
Issue number16
StatePublished - 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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