Sumoylation of RecQ helicase controls the fate of dysfunctional telomeres.
Genome stability depends upon the RecQ helicases, which are conserved from bacteria to man, but little is known about how their myriad activities are regulated. Fission yeast lacking the telomere protein Taz1 (mammalian TRF1/TRF2 ortholog) lose many hallmarks of telomeres, including accurate replication and local protection from DNA repair reactions. Here we show that the RecQ homolog, Rqh1, is sumoylated. Surprisingly, Rqh1 acts on taz1Delta telomeres in a deleterious way, promoting telomere breakage and entanglement. Mutation of Rqh1 sumoylation sites rescues taz1Delta cells from these hazards without dramatically affecting nontelomeric Rqh1 functions. The prominence of Rqh1 in the etiology of several different telomere defects supports the idea that they originate from a common underlying lesion--aberrant processing of the stalled telomeric replication forks that accumulate in the absence of Taz1. Our work underscores the principle that RecQ helicases are "double-edged swords" whose activity, while necessary for maintaining genome-wide stability, must be vigilantly controlled.
Rog
Ofer
O
Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Miller
Kyle M
KM
Ferreira
Miguel Godinho
MG
Cooper
Julia Promisel
JP
D000483:Alleles; D003080:Cold Temperature; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D015966:Gene Expression Regulation, Fungal / Q000528:radiation effects; D042822:Genomic Instability; D005838:Genotype; D009154:Mutation; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D018741:Replication Origin; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000172:deficiency / Q000235:genetics; D013997:Time Factors
D029702:Schizosaccharomyces pombe Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D034501:Telomere-Binding Proteins; C104344:taz1 protein, S pombe; D004265:DNA Helicases; D053484:RecQ Helicases; C106462:Rqh1 protein, S pombe