Developing T lymphocytes are uniquely sensitive to a lack of topoisomerase III alpha

Mönnich, Maren and Hess, Isabell and Wiest, Waltraud and Bachrati, Csanad Z. and Hickson, Ian D. and Schorpp, Michael and Boehm, Thomas (2010) Developing T lymphocytes are uniquely sensitive to a lack of topoisomerase III alpha. European journal of immunology, 40 (9). pp. 2379-2384. ISSN 0014-2980

Full content URL: http://onlinelibrary.wiley.com/doi/10.1002/eji.201...

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Abstract

All organisms possess at least one type IA DNA topoisomerase. These topoisomerases function as part of a DNA structure-specific "dissolvasome," also known as the RTR complex, which has critical functions in faithful DNA replication, recombination, and chromosome segregation. In humans, the heteromeric RTR complex consists of RMI1, RMI2, the Bloom's syndrome gene product (BLM), and topoisomerase 3A (TOP3A) proteins. Here, we describe the identification and characterization of two deleterious mutations in the zebrafish top3a gene that reveal an unexpected tissue-specific requirement of top3a function in developing thymocytes. Deficiency in top3a activates a p53-dependent check-point but does not affect VDJ recombination. Our results suggest that TOP3A could be a candidate gene involved in human primary immunodeficiency syndromes.

Additional Information:All organisms possess at least one type IA DNA topoisomerase. These topoisomerases function as part of a DNA structure-specific "dissolvasome," also known as the RTR complex, which has critical functions in faithful DNA replication, recombination, and chromosome segregation. In humans, the heteromeric RTR complex consists of RMI1, RMI2, the Bloom's syndrome gene product (BLM), and topoisomerase 3A (TOP3A) proteins. Here, we describe the identification and characterization of two deleterious mutations in the zebrafish top3a gene that reveal an unexpected tissue-specific requirement of top3a function in developing thymocytes. Deficiency in top3a activates a p53-dependent check-point but does not affect VDJ recombination. Our results suggest that TOP3A could be a candidate gene involved in human primary immunodeficiency syndromes.
Keywords:topoisomerase III, zebrafish
Subjects:C Biological Sciences > C550 Immunology
C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Life Sciences
ID Code:7271
Deposited On:01 Feb 2013 09:41

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