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bioRxiv · 10.1101/2024.03.12.584701

The histone chaperone CAF-1 maintains the stability of the ribosomal RNA gene cluster by suppressing end resection of replication-associated DNA double-strand breaks.

Sasaki, M.·Kobayashi, T.·Futami, H.
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Abstract

DNA replication-coupled chromatin assembly is crucial to maintain genome integrity. Here, we demonstrate that absence of the budding yeast histone chaperone CAF-1 induces chromosomal ribosomal RNA gene (rDNA) copy number changes as well as the production of extrachromosomal rDNA circles in a manner dependent on Fob1 that causes replication fork arrest in the rDNA, the homologous recombination protein Rad52, and its interaction with Proliferating Cell Nuclear Antigen. CAF-1 deficiency enhances transcription from the regulatory promoter E-pro, contributing to rDNA instability, but it also stabilizes the rDNA independently through its regulation of E-pro. Absence of CAF-1 induces end resection of DNA double-strand breaks (DSBs) formed at arrested replication forks, which are repaired in a manner dependent on the Mre11-Rad50-Xrs2 complex. CAF-1 deficiency causes partial defects in lagging strand synthesis coupled to nucleosome spacing in the rDNA. Our findings suggest that CAF-1 suppresses Rad52-mediated rDNA instability during repair of replication-coupled DSBs.

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Sasaki, M., Kobayashi, T., Futami, H.. 2024-03-12. The histone chaperone CAF-1 maintains the stability of the ribosomal RNA gene cluster by suppressing end resection of replication-associated DNA double-strand breaks.. https://doi.org/10.1101/2024.03.12.584701

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