2025/09/19 by Hajime Futami, Tsugumi Yamaji, Yuko Katayama +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #DNA Repair Mechanisms #Genomics and Chromatin Dynamics #PARP inhibition in cancer therapy
paper · doi:10.1093/nar/gkaf1010
openalex publication_date 2025/09/19 · openalex created_date 2025/11/28 · openalex updated_date 2026/07/29
DNA replication-coupled chromatin assembly is crucial to maintain genome integrity. Here, we demonstrate that the absence of the budding yeast histone chaperone CAF-1 induces the production of extrachromosomal ribosomal RNA gene (rDNA) circles (ERCs), accompanied by chromosomal rDNA copy number changes, in a manner dependent on Fob1-mediated DNA replication fork arrest in the rDNA, the homologous recombination (HR) protein Rad52, and its interaction with proliferating cell nuclear antigen. In the caf-1 mutant, ERC production is triggered partly by increased transcription from the regulatory promoter E-pro, but is also affected by defects independent of E-pro misregulation. Absence of CAF-1 accumulates resected DNA double-strand breaks (DSBs) formed at arrested replication forks, repair of which leads to enhanced ERC formation. CAF-1 deficiency causes partial defects in lagging strand synthesis coupled to nucleosome spacing in the rDNA. Our findings suggest that CAF-1 suppresses HR-mediated rDNA instability during repair of replication-coupled DSBs.