Local inhibition of rRNA transcription without nucleolar segregation after targeted ion irradiation of the nucleolus.
Cell Line, Tumor
Cell Nucleolus
/ metabolism
DNA Breaks, Double-Stranded
DNA, Ribosomal
/ genetics
Humans
Nucleolus Organizer Region
/ genetics
Pol1 Transcription Initiation Complex Proteins
/ genetics
Poly (ADP-Ribose) Polymerase-1
/ genetics
RNA, Ribosomal
/ genetics
Transcription, Genetic
/ genetics
DSB
Ion microbeam
Nucleolus
rRNA transcription
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
09 10 2019
09 10 2019
Historique:
received:
21
03
2019
accepted:
29
08
2019
pubmed:
8
9
2019
medline:
21
7
2020
entrez:
8
9
2019
Statut:
epublish
Résumé
Nucleoli have attracted interest for their role as cellular stress sensors and as potential targets for cancer treatment. The effect of DNA double-strand breaks (DSBs) in nucleoli on rRNA transcription and nucleolar organisation appears to depend on the agent used to introduce DSBs, DSB frequency and the presence (or not) of DSBs outside the nucleoli. To address the controversy, we targeted nucleoli with carbon ions at the ion microbeam SNAKE. Localized ion irradiation with 1-100 carbon ions per point (about 0.3-30 Gy per nucleus) did not lead to overall reduced ribonucleotide incorporation in the targeted nucleolus or other nucleoli of the same cell. However, both 5-ethynyluridine incorporation and Parp1 protein levels were locally decreased at the damaged nucleolar chromatin regions marked by γH2AX, suggesting localized inhibition of rRNA transcription. This locally restricted transcriptional inhibition was not accompanied by nucleolar segregation, a structural reorganisation observed after inhibition of rRNA transcription by treatment with actinomycin D or UV irradiation. The presented data indicate that even multiple complex DSBs do not lead to a pan-nucleolar response if they affect only a subnucleolar region.
Identifiants
pubmed: 31492757
pii: jcs.232181
doi: 10.1242/jcs.232181
pmc: PMC6803363
pii:
doi:
Substances chimiques
DNA, Ribosomal
0
Pol1 Transcription Initiation Complex Proteins
0
RNA, Ribosomal
0
transcription factor UBF
0
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2019. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
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