The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Lafuente_Barquero_2017_The_Smc56
Final published version, 6.25 MB, PDF document
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.
Original language | English |
---|---|
Article number | e1007136 |
Journal | PLOS Genetics |
Volume | 13 |
Issue number | 12 |
Number of pages | 25 |
ISSN | 1553-7390 |
DOIs | |
Publication status | Published - 27 Dec 2017 |
Number of downloads are based on statistics from Google Scholar and www.ku.dk
ID: 188270518