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The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage

RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanco...

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Hauptverfasser: Lafuente-Barquero, Juan (VerfasserIn) , Luke-Glaser, Sarah (VerfasserIn) , Luke, Brian (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: December 27, 2017
In: PLoS Genetics
Year: 2017, Jahrgang: 13, Heft: 12
ISSN:1553-7404
DOI:10.1371/journal.pgen.1007136
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.pgen.1007136
Verlag, kostenfrei, Volltext: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007136
Volltext
Verfasserangaben:Juan Lafuente-Barquero, Sarah Luke-Glaser, Marco Graf, Sonia Silva, Belén Gómez-González, Arianna Lockhart, Michael Lisby, Andrés Aguilera, Brian Luke
Beschreibung
Zusammenfassung:RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci. Mph1 forms foci when RNA-DNA hybrids accumulate, e.g. in RNase H or THO-complex mutants and at short telomeres. Mph1, however is a double-edged sword, whose action at hybrids must be regulated by the Smc5/6 complex. This is underlined by the observation that simultaneous inactivation of RNase H2 and Smc5/6 results in Mph1-dependent synthetic lethality, which is likely due to an accumulation of toxic recombination intermediates. The data presented here support a model, where Mph1’s helicase activity plays a crucial role in responding to persistent RNA-DNA hybrids.
Beschreibung:Gesehen am 30.10.2018
Beschreibung:Online Resource
ISSN:1553-7404
DOI:10.1371/journal.pgen.1007136

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