A cohesin/HUSH- and LINC-dependent pathway controls ribosomal DNA double-strand break repair.
Cell Cycle Proteins
/ metabolism
Cell Nucleolus
/ metabolism
Chromosomal Proteins, Non-Histone
/ metabolism
DNA Breaks, Double-Stranded
DNA Repair
/ genetics
DNA, Ribosomal
/ genetics
Gene Expression Regulation
/ genetics
Histones
/ metabolism
Homologous Recombination
/ genetics
Nuclear Envelope
/ metabolism
RNA, Long Noncoding
/ metabolism
Cohesins
DSB repair
HUSH
LINC
chromatin
cohesin
ribosomal DNA
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 09 2019
01 09 2019
Historique:
received:
04
01
2019
accepted:
26
06
2019
pubmed:
10
8
2019
medline:
29
10
2019
entrez:
10
8
2019
Statut:
ppublish
Résumé
The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. DNA double-strand breaks (DSBs) within rDNA induce both rDNA transcriptional repression and nucleolar segregation, but the link between the two events remains unclear. Here we found that DSBs induced on rDNA trigger transcriptional repression in a cohesin- and HUSH (human silencing hub) complex-dependent manner throughout the cell cycle. In S/G2 cells, transcriptional repression is further followed by extended resection within the interior of the nucleolus, DSB mobilization at the nucleolar periphery within nucleolar caps, and repair by homologous recombination. We showed that nuclear envelope invaginations frequently connect the nucleolus and that rDNA DSB mobilization, but not transcriptional repression, involves the nuclear envelope-associated LINC complex and the actin pathway. Altogether, our data indicate that rDNA break localization at the nucleolar periphery is not a direct consequence of transcriptional repression but rather is an active process that shares features with the mobilization of persistent DSB in active genes and heterochromatin.
Identifiants
pubmed: 31395742
pii: gad.324012.119
doi: 10.1101/gad.324012.119
pmc: PMC6719620
doi:
Substances chimiques
Cell Cycle Proteins
0
Chromosomal Proteins, Non-Histone
0
DNA, Ribosomal
0
Histones
0
RNA, Long Noncoding
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1175-1190Informations de copyright
© 2019 Marnef et al.; Published by Cold Spring Harbor Laboratory Press.
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