FLASH degradation in response to UV-C results in histone locus bodies disruption and cell-cycle arrest.

Oncogene
L Bongiorno-BorboneV De Laurenzi

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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Citations

Dec 2, 2010·Molecular Biology of the Cell·Marc-David RueppDaniel Schümperli
Feb 23, 2011·Molecular Cancer·Anne Hege Alm-KristiansenOdd S Gabrielsen
Feb 20, 2016·Current Opinion in Cell Biology·Valentina Romeo, Daniel Schümperli
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Oct 23, 2010·Molecular Cell·Séverine BoulonAngus I Lamond
May 16, 2017·Journal of Cellular Physiology·Andrew J FritzGary S Stein
Jul 1, 2016·The EMBO Journal·Edward M CourchaineKarla M Neugebauer
Feb 24, 2018·Biochemistry·Dahyana Arias Escayola, Karla M Neugebauer

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