Holliday junction-containing DNA structures persist in cells lacking Sgs1 or Top3 following exposure to DNA damage

The Sgs1-Rmi1-Top3 "dissolvasome" is required for the maintenance of genome stability and has been implicated in the processing of various types of DNA structures arising during DNA replication. Previous investigations have revealed that unprocessed (X-shaped) homologous recombination repa...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS Jg. 108; H. 12; S. 4944
Hauptverfasser: Mankouri, Hocine W, Ashton, Thomas M, Hickson, Ian D
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 22.03.2011
Schlagworte:
DNA Damage - drug effects
DNA Damage - physiology
DNA, Cruciform - genetics
DNA, Cruciform - metabolism
DNA, Fungal - genetics
DNA, Fungal - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Escherichia coli Proteins - genetics
Escherichia coli Proteins - metabolism
Holliday Junction Resolvases - genetics
Holliday Junction Resolvases - metabolism
Humans
Methyl Methanesulfonate - pharmacology
Mutagens - pharmacology
RecQ Helicases - genetics
RecQ Helicases - metabolism
S Phase - drug effects
S Phase - physiology
Saccharomyces cerevisiae - enzymology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
ISSN:1091-6490, 1091-6490
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The Sgs1-Rmi1-Top3 "dissolvasome" is required for the maintenance of genome stability and has been implicated in the processing of various types of DNA structures arising during DNA replication. Previous investigations have revealed that unprocessed (X-shaped) homologous recombination repair (HRR) intermediates persist when S-phase is perturbed by using methyl methanesulfonate (MMS) in Saccharomyces cerevisiae cells with impaired Sgs1 or Top3. However, the precise nature of these persistent DNA structures remains poorly characterized. Here, we report that ectopic expression of either of two heterologous and structurally unrelated Holliday junction (HJ) resolvases, Escherichia coli RusA or human GEN1(1-527), promotes the removal of these X-structures in vivo. Moreover, other types of DNA replication intermediates, including stalled replication forks and non-HRR-dependent X-structures, are refractory to RusA or GEN1(1-527), demonstrating specificity of these HJ resolvases for MMS-induced X-structures in vivo. These data suggest that the X-structures persisting in cells with impaired Sgs1 or Top3 contain HJs. Furthermore, we demonstrate that Sgs1 directly promotes X-structure removal, because the persistent structures arising in Sgs1-deficient strains are eliminated when Sgs1 is reactivated in vivo. We propose that HJ resolvases and Sgs1-Top3-Rmi1 comprise two independent processes to deal with HJ-containing DNA intermediates arising during HRR in S-phase.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1014240108