USP42 enhances homologous recombination repair by promoting R-loop resolution with a DNA-RNA helicase DHX9.

ABSTRACT: The nucleus of mammalian cells is compartmentalized by nuclear bodies such as nuclear speckles, however, involvement of nuclear bodies, especially nuclear speckles, in DNA repair has not been actively investigated. Here, our focused screen for nuclear speckle factors involved in homologous recombination (HR), which is a faithful DNA double-strand break (DSB) repair mechanism, identified transcription-related nuclear speckle factors as potential HR regulators. Among the top hits, we provide evidence showing that USP42, which is a hitherto unidentified nuclear speckles protein, promotes HR by facilitating BRCA1 recruitment to DSB sites and DNA-end resection. We further showed that USP42 localization to nuclear speckles is required for efficient HR. Furthermore, we established that USP42 inte

SUBMITTER: Matsui M 

PROVIDER: S-EPMC7296013 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature