Developing T lymphocytes are uniquely sensitive to a lack of topoisomerase III alpha
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Developing T lymphocytes are uniquely sensitive to a lack of topoisomerase III alpha. / Mönnich, Maren; Hess, Isabell; Wiest, Waltraud; Bachrati, Csanad; Hickson, Ian D; Schorpp, Michael; Boehm, Thomas.
In: European Journal of Immunology, Vol. 40, No. 9, 09.2010, p. 2379-84.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Developing T lymphocytes are uniquely sensitive to a lack of topoisomerase III alpha
AU - Mönnich, Maren
AU - Hess, Isabell
AU - Wiest, Waltraud
AU - Bachrati, Csanad
AU - Hickson, Ian D
AU - Schorpp, Michael
AU - Boehm, Thomas
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - Animals
KW - CD4-Positive T-Lymphocytes
KW - Cell Differentiation
KW - DNA Breaks, Double-Stranded
KW - DNA Topoisomerases, Type I
KW - Homeodomain Proteins
KW - Humans
KW - In Situ Hybridization
KW - Models, Molecular
KW - Protein Binding
KW - Sequence Alignment
KW - Sequence Deletion
KW - Tumor Suppressor Protein p53
KW - Zebrafish
KW - Zebrafish Proteins
U2 - 10.1002/eji.201040634
DO - 10.1002/eji.201040634
M3 - Journal article
C2 - 20623552
VL - 40
SP - 2379
EP - 2384
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 9
ER -
ID: 32318803