Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1

Yang, Jay and Bachrati, Csanad and Ou, Jiongwen and Hickson, Ian D. and Brown, Grant W. (2010) Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1. The Journal of biological chemistry, 285 (28). pp. 21426-21436. ISSN 0021-9258

Full content URL: http://www.jbc.org/content/285/28/21426

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Abstract

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.

Additional Information: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.
Keywords:topoisomerase III, Replication protein A, RPA, DNA decatenation, double Holliday junction dissolution
Subjects:C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Life Sciences
ID Code:7272
Deposited On:01 Feb 2013 09:23

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