Reversible Top1 cleavage complexes are stabilized strand-specifically at the ribosomal replication fork barrier and contribute to ribosomal DNA stability.

Détails

Ressource 1Télécharger: BIB_4C4A5F4406DC.P001.pdf (7759.94 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_4C4A5F4406DC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Reversible Top1 cleavage complexes are stabilized strand-specifically at the ribosomal replication fork barrier and contribute to ribosomal DNA stability.
Périodique
Nucleic Acids Research
Auteur(s)
Krawczyk C., Dion V., Schär P., Fritsch O.
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Statut éditorial
Publié
Date de publication
2014
Volume
42
Numéro
8
Pages
4985-4995
Langue
anglais
Résumé
Various topological constraints at the ribosomal DNA (rDNA) locus impose an extra challenge for transcription and DNA replication, generating constant torsional DNA stress. The topoisomerase Top1 is known to release such torsion by single-strand nicking and re-ligation in a process involving transient covalent Top1 cleavage complexes (Top1cc) with the nicked DNA. Here we show that Top1ccs, despite their usually transient nature, are specifically targeted to and stabilized at the ribosomal replication fork barrier (rRFB) of budding yeast, establishing a link with previously reported Top1 controlled nicks. Using ectopically engineered rRFBs, we establish that the rRFB sequence itself is sufficient for induction of DNA strand-specific and replication-independent Top1ccs. These Top1ccs accumulate only in the presence of Fob1 and Tof2, they are reversible as they are not subject to repair by Tdp1- or Mus81-dependent processes, and their presence correlates with Top1 provided rDNA stability. Notably, the targeted formation of these Top1ccs accounts for the previously reported broken replication forks at the rRFB. These findings implicate a novel and physiologically regulated mode of Top1 action, suggesting a mechanism by which Top1 is recruited to the rRFB and stabilized in a reversible Top1cc configuration to preserve the integrity of the rDNA.
Mots-clé
UI="D053903">DNA Breaks, Double-Stranded, UI="D053837">DNA Cleavage, UI="D004261">DNA Replication, UI="D004264">DNA Topoisomerases, Type I/UI="Q000378">metabolism, UI="D004275">DNA, Ribosomal/UI="Q000096">biosynthesis, UI="D004275">DNA, Ribosomal/UI="Q000378">metabolism, UI="D004268">DNA-Binding Proteins/UI="Q000378">metabolism, UI="D047908">Intracellular Signaling Peptides and Proteins/UI="Q000378">metabolism, UI="D055550">Protein Stability, UI="D053484">RecQ Helicases/UI="Q000235">genetics, UI="D029701">Saccharomyces cerevisiae Proteins/UI="Q000235">genetics, UI="D029701">Saccharomyces cerevisiae Proteins/UI="Q000378">metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
16/12/2014 14:28
Dernière modification de la notice
20/08/2019 14:00
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