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Pre-rRNA facilitates the recruitment of RAD51AP1 to DNA double-strand breaks.

ABSTRACT: RAD51-associated protein 1 (RAD51AP1) is known to promote homologous recombination (HR) repair. However, the precise mechanism of RAD51AP1 in HR repair is unclear. Here, we identify that RAD51AP1 associates with pre-rRNA. Both the N terminus and C terminus of RAD51AP1 recognize pre-rRNA. Pre-rRNA not only colocalizes with RAD51AP1 at double-strand breaks (DSBs) but also facilitates the recruitment of RAD51AP1 to DSBs. Consistently, transient inhibition of pre-rRNA synthesis by RNA polymerase I inhibitor suppresses the recruitment of RAD51AP1 as well as HR repair. Moreover, RAD51AP1 forms liquid-liquid phase separation in the presence of pre-rRNA in vitro, which may be the molecular mechanism of RAD51AP1 foci formation. Taken together, our results demonstrate that pre-rRNA mediates the relocation of RAD51AP1 to DSBs for HR repair.

SUBMITTER: Chen L

PROVIDER: S-EPMC10959706 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Pre-rRNA facilitates the recruitment of RAD51AP1 to DNA double-strand breaks.

Chen Linlin L Gai Xiaochen X Yu Xiaochun X

The Journal of biological chemistry 20240224 3

RAD51-associated protein 1 (RAD51AP1) is known to promote homologous recombination (HR) repair. However, the precise mechanism of RAD51AP1 in HR repair is unclear. Here, we identify that RAD51AP1 associates with pre-rRNA. Both the N terminus and C terminus of RAD51AP1 recognize pre-rRNA. Pre-rRNA not only colocalizes with RAD51AP1 at double-strand breaks (DSBs) but also facilitates the recruitment of RAD51AP1 to DSBs. Consistently, transient inhibition of pre-rRNA synthesis by RNA polymerase I i ...[more]

PMID: 38403248

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2025-05-06 | PXD048694 | Pride

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