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

被引：21

作者：

Bongiorno-Borbone, L. ^{[2
]}

De Cola, A. ^{[2
]}

Barcaroli, D. ^{[2
,3
]}

Knight, R. A. ^{[4
]}

Di Ilio, C. ^{[3
]}

Melino, G. ^{[2
,4
]}

De Laurenzi, V. ^{[1
,3
]}

机构：

[1] Univ G DAnnunzio, Dipartimento Sci Biomed, CeSI, I-66100 Chieti, Italy

[2] Univ Roma Tor Vergata, Dept Expt Med, IDI IRCCS Biochem Lab, Rome, Italy

[3] Fdn G DAnnunzio, Ctr Studi SullInvecchiamento, Chieti, Italy

[4] Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England

来源：

ONCOGENE | 2010年 / 29卷 / 06期

关键词：

histone locus bodies; Cajal bodies; UV; FLASH; S-PHASE PROGRESSION; DNA-DAMAGE; CAJAL BODIES; GENE-EXPRESSION; E/CDK2; SUBSTRATE; TRANSCRIPTION; P220(NPAT); CHECKPOINT; G(1); BODY;

D O I：

10.1038/onc.2009.388

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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. Oncogene (2010) 29, 802-810; doi:10.1038/onc.2009.388; published online 16 November 2009

引用

页码：802 / 810

页数：9

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