Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair.
The evolutionarily conserved Smc5/6 complex is implicated in recombinational repair, but its function in this process has been elusive. Here we report that the budding yeast Smc5/6 complex directly binds to the DNA helicase Mph1. Mph1 and its helicase activity define a replication-associated recombination subpathway. We show that this pathway is toxic when the Smc5/6 complex is defective, because mph1Delta and its helicase mutations suppress multiple defects in mutants of the Smc5/6 complex, including their sensitivity to replication-blocking agents, growth defects, and inefficient chromatid separation, whereas MPH1 overexpression exacerbates some of these defects. We further demonstrate that Mph1 and its helicase activity are largely responsible for the accumulation of potentially deleterious recombination intermediates in mutants of the Smc5/6 complex. We also present evidence that mph1Delta does not alleviate sensitivity to DNA damage or the accumulation of recombination intermediates in cells lacking Sgs1, which is thought to function together with the Smc5/6 complex. Thus, our results reveal a function of the Smc5/6 complex in the Mph1-dependent recombinational subpathway that is distinct from Sgs1. We suggest that the Smc5/6 complex can counteract/modulate a pro-recombinogenic function of Mph1 or facilitate the resolution of recombination structures generated by Mph1.
Chen
Yu-Hung
YH
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Choi
Koyi
K
Szakal
Barnabas
B
Arenz
Jacqueline
J
Duan
Xinyuan
X
Ye
Hong
H
Branzei
Dana
D
Zhao
Xiaolan
X
D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D050505:Mutant Proteins; D053484:RecQ Helicases / Q000502:physiology; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D004718:Saccharomycetales / Q000235:genetics* / Q000254:growth & development
D018797:Cell Cycle Proteins; D050505:Mutant Proteins; C486627:SMC5 protein, S cerevisiae; C486631:SMC6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C491240:MPH1 protein, S cerevisiae; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases; D053487:DEAD-box RNA Helicases