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...

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Vydáno v:	Proceedings of the National Academy of Sciences - PNAS Ročník 108; číslo 12; s. 4944
Hlavní autoři:	Mankouri, Hocine W, Ashton, Thomas M, Hickson, Ian D
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 22.03.2011
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1091-6490 1091-6490
DOI:	10.1073/pnas.1014240108