NAKADA Shinichiro ≪Bioregulation and Cellular Response≫ “Fine-tuning of DNA damage-dependent ubiquitination by OTUB2 supports the DNA repair pathway choice”

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PublishMolecular Cell(2014) doi:10.1016/j.molcel.2014.01.030

DNA double-strand breaks (DSBs) are deleterious lesions that lead to genetic mutations and cell death. Most of DSBs are repaired by homologous recombination or non-homologous end joining. Accumulating evidences suggest that DNA repair pathway choice is an important mechanism for maintaining genomic stability. In this study, we revealed that the deubiquitinating enzyme OTUB2 fine-tunes the speed of DSB-induced ubiquitination so that the appropriate DNA repair pathway is chosen. Depletion of OTUB2 enhances DSB-induced ubiquitination and accelerates accumulation of 53BP1 and RAP80 at DSBs, which in turn inhibits homologous recombination and promotes non-homologous end joining. OTUB2 suppress excessive ubiquitination and enables homologous recombination.