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 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. © 2017 lafuente-barquero et al.