RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex.
SGS1 encodes a DNA helicase whose homologues in human cells include the BLM, WRN, and RECQ4 genes, mutations in which lead to cancer-predisposition syndromes. Clustering of synthetic genetic interactions identified by large-scale genetic network analysis revealed that the genetic interaction profile of the gene RMI1 (RecQ-mediated genome instability, also known as NCE4 and YPL024W) was highly similar to that of SGS1 and TOP3, suggesting a functional relationship between Rmi1 and the Sgs1/Top3 complex. We show that Rmi1 physically interacts with Sgs1 and Top3 and is a third member of this complex. Cells lacking RMI1 activate the Rad53 checkpoint kinase, undergo a mitotic delay, and display increased relocalization of the recombination repair protein Rad52, indicating the presence of spontaneous DNA damage. Consistent with a role for RMI1 in maintaining genome integrity, rmi1Delta cells exhibit increased recombination frequency and increased frequency of gross chromosomal rearrangements. In addition, rmi1Delta strains fail to fully activate Rad53 upon exposure to DNA-damaging agents, suggesting that Rmi1 is also an important part of the Rad53-dependent DNA damage response.
Chang
Michael
M
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
Bellaoui
Mohammed
M
Zhang
Chaoying
C
Desai
Ridhdhi
R
Morozov
Pavel
P
Delgado-Cruzata
Lissette
L
Rothstein
Rodney
R
Freyer
Greg A
GA
Boone
Charles
C
Brown
Grant W
GW
D000251:Adenosine Triphosphatases / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D019143:Evolution, Molecular; D018816:Genes, cdc; D016681:Genome, Fungal; D046912:Multiprotein Complexes; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D051721:Rad52 DNA Repair and Recombination Protein; D053484:RecQ Helicases; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; C502206:Rmi1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C502374:TOP3 protein, S cerevisiae; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C090472:SGS1 protein, S cerevisiae; D004265:DNA Helicases; D053484:RecQ Helicases