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

European Journal of Immunology
Maren MönnichThomas Boehm

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.

References

Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·W Li, J C Wang
Jul 11, 2000·Clinical and Experimental Immunology·A R GenneryP A Jeggo
May 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·K Y Kwan, J C Wang
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·James C Wang
Jul 6, 2002·Science·Erno WienholdsRonald H A Plasterk
Feb 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kelvin Y KwanJames C Wang
Aug 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael SchorppThomas Boehm
May 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kelvin Y KwanJames C Wang
Nov 6, 2007·Trends in Biochemical Sciences·Hocine W Mankouri, Ian D Hickson
Feb 18, 2009·The Journal of Experimental Medicine·Beth A HelminkBarry P Sleckman
Sep 8, 2009·Advances in Experimental Medicine and Biology·Jean-Pierre de Villartay
Jan 1, 2010·The Journal of Allergy and Clinical Immunology·Luigi D Notarangelo

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Citations

Jan 10, 2012·Disease Models & Mechanisms·Stephen A Renshaw, Nikolaus S Trede
Mar 19, 2013·Annual Review of Biochemistry·Stefanie Hartman ChenTao-shih Hsieh
Jun 19, 2012·Annual Review of Genomics and Human Genetics·Thomas BoehmIsabell Hess
May 13, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Norimasa IwanamiThomas Boehm
Aug 29, 2019·International Journal of Molecular Sciences·Baubak BajoghliNarges Aghaallaei
Jan 28, 2021·Nature Communications·Ann-Marie K ShorrocksAndrew N Blackford

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