Fanconi Anemia Is Characterized by Delayed Repair Kinetics of DNA Double-Strand Breaks
2010
Authors
Leskovac, AndrejaVujić, Dragana
Guć-Šćekić, Marija
Petrović, Sandra
Joksić, Ivana
Slijepcevic, Predrag
Joksić, Gordana
Article
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Among patients with bone marrow failure (BMF) syndrome, some are happened to have underlying Fanconi anemia (FA), a genetically heterogeneous disease, which is characterized by progressive pancytopenia and cancer susceptibility. Due to heterogeneous nature of the disease, a single genetic test, as in vitro response to DNA cross-linking agents, usually is not enough to make correct diagnosis. The aim of this study was to evaluate whether measuring repair kinetics of radiation-induced DNA double-strand breaks (DSBs) can distinguish Fanconi anemia from other BMF patients. An early step in repair of DSBs is phosphorylation of the histone H2AX, generating gamma-H2AX histone, which extends over mega base-pair regions of DNA from the break site and is visualised as foci (gamma-H2AX foci) with specific antibodies. The primary fibroblasts, established from FA patients, were exposed to gamma-rays, a dose of 2 Gy (Co-60), incubated for up to 24 hours under repair-permissive conditions, and assaye...d for the level of gamma-H2AX foci and apoptosis at different recovery times after the treatment. Cell lines originating from FA patients displayed a significant delay in the repair of radiation-induced DNA DSBs relative to non-FA bone marrow failure (non-FA BMF) and control cell lines. The delay is especially evident at recovery time of 24 hours, and is seen as about 8-fold increase of residual gamma-H2AX foci compared to self-state before irradiation. The delay in repair kinetics of FA cells represents the unique feature of FA cellular phenotype, which should be exploited to distinguish FA cellular phenotype.
Keywords:
double-strand breaks / repair kinetics / gamma-H2AX foci / apoptosis / irradiationSource:
Tohoku Journal of Experimental Medicine, 2010, 221, 1, 69-76Funding / projects:
- Serbian Ministry of Science and Technological Development [143046]
DOI: 10.1620/tjem.221.69
ISSN: 0040-8727; 1349-3329
PubMed: 20453460
WoS: 000277671800010
Scopus: 2-s2.0-77951710441
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VinčaTY - JOUR AU - Leskovac, Andreja AU - Vujić, Dragana AU - Guć-Šćekić, Marija AU - Petrović, Sandra AU - Joksić, Ivana AU - Slijepcevic, Predrag AU - Joksić, Gordana PY - 2010 UR - https://vinar.vin.bg.ac.rs/handle/123456789/4000 AB - Among patients with bone marrow failure (BMF) syndrome, some are happened to have underlying Fanconi anemia (FA), a genetically heterogeneous disease, which is characterized by progressive pancytopenia and cancer susceptibility. Due to heterogeneous nature of the disease, a single genetic test, as in vitro response to DNA cross-linking agents, usually is not enough to make correct diagnosis. The aim of this study was to evaluate whether measuring repair kinetics of radiation-induced DNA double-strand breaks (DSBs) can distinguish Fanconi anemia from other BMF patients. An early step in repair of DSBs is phosphorylation of the histone H2AX, generating gamma-H2AX histone, which extends over mega base-pair regions of DNA from the break site and is visualised as foci (gamma-H2AX foci) with specific antibodies. The primary fibroblasts, established from FA patients, were exposed to gamma-rays, a dose of 2 Gy (Co-60), incubated for up to 24 hours under repair-permissive conditions, and assayed for the level of gamma-H2AX foci and apoptosis at different recovery times after the treatment. Cell lines originating from FA patients displayed a significant delay in the repair of radiation-induced DNA DSBs relative to non-FA bone marrow failure (non-FA BMF) and control cell lines. The delay is especially evident at recovery time of 24 hours, and is seen as about 8-fold increase of residual gamma-H2AX foci compared to self-state before irradiation. The delay in repair kinetics of FA cells represents the unique feature of FA cellular phenotype, which should be exploited to distinguish FA cellular phenotype. T2 - Tohoku Journal of Experimental Medicine T1 - Fanconi Anemia Is Characterized by Delayed Repair Kinetics of DNA Double-Strand Breaks VL - 221 IS - 1 SP - 69 EP - 76 DO - 10.1620/tjem.221.69 ER -
@article{ author = "Leskovac, Andreja and Vujić, Dragana and Guć-Šćekić, Marija and Petrović, Sandra and Joksić, Ivana and Slijepcevic, Predrag and Joksić, Gordana", year = "2010", abstract = "Among patients with bone marrow failure (BMF) syndrome, some are happened to have underlying Fanconi anemia (FA), a genetically heterogeneous disease, which is characterized by progressive pancytopenia and cancer susceptibility. Due to heterogeneous nature of the disease, a single genetic test, as in vitro response to DNA cross-linking agents, usually is not enough to make correct diagnosis. The aim of this study was to evaluate whether measuring repair kinetics of radiation-induced DNA double-strand breaks (DSBs) can distinguish Fanconi anemia from other BMF patients. An early step in repair of DSBs is phosphorylation of the histone H2AX, generating gamma-H2AX histone, which extends over mega base-pair regions of DNA from the break site and is visualised as foci (gamma-H2AX foci) with specific antibodies. The primary fibroblasts, established from FA patients, were exposed to gamma-rays, a dose of 2 Gy (Co-60), incubated for up to 24 hours under repair-permissive conditions, and assayed for the level of gamma-H2AX foci and apoptosis at different recovery times after the treatment. Cell lines originating from FA patients displayed a significant delay in the repair of radiation-induced DNA DSBs relative to non-FA bone marrow failure (non-FA BMF) and control cell lines. The delay is especially evident at recovery time of 24 hours, and is seen as about 8-fold increase of residual gamma-H2AX foci compared to self-state before irradiation. The delay in repair kinetics of FA cells represents the unique feature of FA cellular phenotype, which should be exploited to distinguish FA cellular phenotype.", journal = "Tohoku Journal of Experimental Medicine", title = "Fanconi Anemia Is Characterized by Delayed Repair Kinetics of DNA Double-Strand Breaks", volume = "221", number = "1", pages = "69-76", doi = "10.1620/tjem.221.69" }
Leskovac, A., Vujić, D., Guć-Šćekić, M., Petrović, S., Joksić, I., Slijepcevic, P.,& Joksić, G.. (2010). Fanconi Anemia Is Characterized by Delayed Repair Kinetics of DNA Double-Strand Breaks. in Tohoku Journal of Experimental Medicine, 221(1), 69-76. https://doi.org/10.1620/tjem.221.69
Leskovac A, Vujić D, Guć-Šćekić M, Petrović S, Joksić I, Slijepcevic P, Joksić G. Fanconi Anemia Is Characterized by Delayed Repair Kinetics of DNA Double-Strand Breaks. in Tohoku Journal of Experimental Medicine. 2010;221(1):69-76. doi:10.1620/tjem.221.69 .
Leskovac, Andreja, Vujić, Dragana, Guć-Šćekić, Marija, Petrović, Sandra, Joksić, Ivana, Slijepcevic, Predrag, Joksić, Gordana, "Fanconi Anemia Is Characterized by Delayed Repair Kinetics of DNA Double-Strand Breaks" in Tohoku Journal of Experimental Medicine, 221, no. 1 (2010):69-76, https://doi.org/10.1620/tjem.221.69 . .