RAD54L coordinates the nucleolar DNA damage response to maintain rDNA stability

ABSTRACT: The nucleolus is organized around actively transcribed ribosomal RNA genes (rDNA), where high RNA polymerase I (Pol I) activity creates intrinsic susceptibility to replication stress and DNA damage. Here, we identify the DNA translocase RAD54L as a critical regulator of the nucleolar DNA damage response (nDDR) to rDNA double strand breaks (DSBs) and replication stress. We show that RAD54L localizes to the nucleolus under basal conditions and is recruited to nucleolar caps following CRISPR-Cas9-induced rDNA DSBs to promote repair. RAD54L loss results in persistent RAD51 foci, increased γH2AX and micronuclei formation, indicating defective resolution of rDNA lesions and genome instability. Under baseline conditions and replication stress induced by the Pol I transcription inhibitor CX-5461,

SUBMITTER: Ruofei Liu 

PROVIDER: S-SCDT-10_1038-S44318-026-00864-3 | biostudies-other |

REPOSITORIES: biostudies-other