PUBLICATION

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

Authors
Mönnich, M., Hess, I., Wiest, W., Bachrati, C., Hickson, I.D., Schorpp, M., and Boehm, T.
ID
ZDB-PUB-100719-44
Date
2010
Source
European journal of immunology   40(9): 2379-2384 (Journal)
Registered Authors
Boehm, Tom, Hess, Isabell, Monnich, Maren, Schorpp, Michael, Wiest, Waltraud
Keywords
thymopoiesis, topoisomerase IIIa, mutation, zebrafish
MeSH Terms
  • Animals
  • CD4-Positive T-Lymphocytes
  • Cell Differentiation/genetics
  • DNA Breaks, Double-Stranded*
  • DNA Topoisomerases, Type I/genetics
  • DNA Topoisomerases, Type I/immunology
  • DNA Topoisomerases, Type I/metabolism*
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/immunology
  • Homeodomain Proteins/metabolism*
  • Humans
  • In Situ Hybridization
  • Models, Molecular
  • Protein Binding
  • Sequence Alignment
  • Sequence Deletion
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/immunology
  • Tumor Suppressor Protein p53/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/immunology
  • Zebrafish Proteins/metabolism*
PubMed
20623552 Full text @ Eur. J. Immunol.
Abstract
All organisms possess at least one typeDNA 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 top3agene 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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes