{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316591/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316591"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Treacle-dependent TOPBP1 condensation regulates the nucleolar DNA damage response.","description":"We show that Treacle promotes phase separation of TOPBP1 within the FC to initiate spatially confined n-DDR signaling and to direct rDNA repair pathway choice. Using both a reductionist FKBP-based system for inducible TOPBP1 oligomerization and physiological models of genotoxic rDNA damage, we demonstrate that phosphorylation of Treacle at Ser1191 by CK2 and at Ser1199 by ATR/ATM enables bivalent engagement of the BRCT2 and BRCT5 domains of TOPBP1, thereby nucleating Treacle-dependent TOPBP1 condensation. This condensate is further stabilized by TOPBP1 oligomerization via its BRCT7/8 domains, giving rise to a nested, “Russian doll”-like phase architecture that spatially and temporally compartmentalizes DDR signaling within the nucleolus. Functionally, Treacle-dependent TOPBP1 condensation initiates γH2AX signaling and promotes recruitment of DNA repair factors in a stress-dependent manner. Importantly, disruption of this condensation does not abolish rDNA double-strand break repair but biases repair toward rapid DNA-PK–dependent non-homologous end joining, while impairing ATR/ATM activation and late-phase homologous recombination–associated repair. Consistent with this, Treacle-knockout cells exhibit accelerated early rDNA repair kinetics but incomplete damage resolution at later stages. Together, our findings identify Treacle as a molecular platform that coordinates TOPBP1 condensation, nucleolar DDR signaling, and rDNA repair pathway choice, and establish phase separation as a central organizing principle underlying functional specialization of the nucleolar DNA damage response.","dates":{"publication":"2026/05/27"},"accession":"GSE316591","cross_references":{"GSM":["GSM9456647","GSM9456648","GSM9456649"],"GPL":["20301"],"GSE":["316591"],"taxon":["Homo sapiens"],"PMID":["[42152682]"]}}