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bioRxiv · 10.1101/2025.11.01.686071

Fission yeast histone chaperone Rtt106 regulates histone levels, prevents early division, and promotes genome stability

Sanayhie, S. A.·Da Pra, V. A.·Khodabakhshian, N.·Karam, E.·Chhipa, M. A.·Kang, S.·Ahmed, A.·Fillingham, J.·Sabatinos, S. A.
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Abstract

Chromatin packaging influences gene expression and is linked to genome stability through the establishment and maintenance of histone modifications. Histone chaperone proteins regulate chromatin assembly and thus packaging. We tested how loss of the histone chaperone Rtt106 affects genome stability through cell cycle checkpoint stability in response to cellular stress. We tested how double mutants lacking DNA replication or DNA damage checkpoint kinases are impacted by the absence of histone chaperone rtt106. Rtt106 brings histone H3 and histone H4 together into complexes. We found that rtt106{Delta} cells with loss of the DNA replication checkpoint (cds1{Delta}, rad3{Delta}) were more sensitive to hydroxyurea. However, DNA damage kinase chk1{Delta} rtt106{Delta} cells became less sensitive to DNA damaging drugs. The effects of Rtt106 on growth are observed in division timing, where rtt106{Delta} cells show early division in the presence of drug. Coupled to a decrease in histone H3 levels and increased mutation rate, our work shows how non-essential Rtt106 activities contribute to genome stability. By regulating histone levels and use, Rtt106 regulates the cell division and may function in chromatin arm coherence and segregation.

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Sanayhie, S. A., Da Pra, V. A., Khodabakhshian, N., Karam, E., Chhipa, M. A., Kang, S., Ahmed, A., Fillingham, J., Sabatinos, S. A.. 2025-11-02. Fission yeast histone chaperone Rtt106 regulates histone levels, prevents early division, and promotes genome stability. https://doi.org/10.1101/2025.11.01.686071

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