Abstract
Eucaryotic cell nuclei contain a number of different organelles that are highly dynamic structures and respond to a variety of stimuli. Here we investigated the effect of UV irradiation on a recently identified group of organelles, Histone Locus Bodies. Histone Locus Bodies contain at least two main proteins, FLASH and NPAT, and have been shown to be involved in replication-dependent histone gene transcription. We show that these organelles are disrupted after sublethal irradiation and both FLASH and NPAT are degraded, which in turn results in cell-cycle arrest at the S/G2 transition. The effect on the cell cycle is due to reduced transcription of histone genes and restoring normal histone protein levels by stabilizing histone mRNA allows cells to progress through the cell cycle. This provides a novel mechanism of S-phase arrest in response to DNA damage that potentially allows DNA repair before cells continue into mitosis, and thus prevents transmission of genomic alterations.
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Acknowledgements
We thank Peter D Adams for the SLBP expression plasmid. The work was supported by grants from AIRC, MIUR to VDL, AIRC, EU-EPISTEM, FIRB, MIUR, MinSan, Telethon and Alleanza Contro il Cancro to GM. DB was supported by an FIRC scholarship.
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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)
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Bongiorno-Borbone, L., De Cola, A., Barcaroli, D. et al. FLASH degradation in response to UV-C results in histone locus bodies disruption and cell-cycle arrest. Oncogene 29, 802–810 (2010). https://doi.org/10.1038/onc.2009.388
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DOI: https://doi.org/10.1038/onc.2009.388
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