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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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 27, 2017
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| In: |
PLoS Genetics
Year: 2017, Volume: 13, Issue: 12 |
| ISSN: | 1553-7404 |
| DOI: | 10.1371/journal.pgen.1007136 |
| Online Access: | 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 
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| Author Notes: | Juan Lafuente-Barquero, Sarah Luke-Glaser, Marco Graf, Sonia Silva, Belén Gómez-González, Arianna Lockhart, Michael Lisby, Andrés Aguilera, Brian Luke |
| Summary: | 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. |
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| Item Description: | Gesehen am 30.10.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1553-7404 |
| DOI: | 10.1371/journal.pgen.1007136 |