HERC2 inactivation abrogates nucleolar localization of RecQ helicases BLM and WRN.

ABSTRACT: The nucleolus is a nuclear structure composed of ribosomal DNA (rDNA), and functions as a site for rRNA synthesis and processing. The rDNA is guanine-rich and prone to form G-quadruplex (G4), a secondary structure of DNA. We have recently found that HERC2, an HECT ubiquitin ligase, promotes BLM and WRN RecQ DNA helicases to resolve the G4 structure. Here, we report the role of HERC2 in the regulation of nucleolar localization of the helicases. Furthermore, HERC2 inactivation enhances the effects of CX-5461, an inhibitor of RNA polymerase I (Pol I)-mediated transcription of rRNA with an intrinsic G4-stabilizing activity. HERC2 depletion or homozygous deletion of the C-terminal HECT domain of HERC2 prevented the nucleolar localization of BLM and WRN, and inhibited relocalization of BLM to re

SUBMITTER: Zhu M 

PROVIDER: S-EPMC7801386 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature