Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1.
Human topoisomerase IIIalpha is a type IA DNA topoisomerase that functions with BLM and RMI1 to resolve DNA replication and recombination intermediates. BLM, human topoisomerase IIIalpha, and RMI1 catalyze the dissolution of double Holliday junctions into noncrossover products via a strand-passage mechanism. We generated single-stranded catenanes that resemble the proposed dissolution intermediate recognized by human topoisomerase IIIalpha. We demonstrate that human topoisomerase IIIalpha is a single-stranded DNA decatenase that is specifically stimulated by the BLM-RMI1 pair. In addition, RMI1 interacts with human topoisomerase IIIalpha, and the interaction is required for the stimulatory effect of RMI1 on decatenase activity. Our data provide direct evidence that human topoisomerase IIIalpha functions as a decatenase with the assistance of BLM and RMI1 to facilitate the processing of homologous recombination intermediates without crossing over as a mechanism to preserve genome integrity.
Yang
Jay
J
Department of Biochemistry and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada and.
Bachrati
Csanad Z
CZ
Ou
Jiongwen
J
Hickson
Ian D
ID
Brown
Grant W
GW
D002352:Carrier Proteins / Q000378:metabolism*; D004249:DNA Damage; D004264:DNA Topoisomerases, Type I / Q000502:physiology*; D045566:DNA, Cruciform / Q000235:genetics; D004277:DNA, Single-Stranded / Q000235:genetics*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary; D053484:RecQ Helicases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D002352:Carrier Proteins; D045566:DNA, Cruciform; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C501527:RMI1 protein, human; C097151:Bloom syndrome protein; D053484:RecQ Helicases; D004264:DNA Topoisomerases, Type I
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