The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
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Fanconi Anemia Is Characterized by Delayed Repair Kinetics of DNA Double-Strand Breaks
Andreja LeskovacDragana VujicMarija Guc-ScekicSandra PetrovicIvana JoksicPredrag SlijepcevicGordana Joksic
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2010 Volume 221 Issue 1 Pages 69-76

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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 γ-H2AX histone, which extends over mega base-pair regions of DNA from the break site and is visualised as foci (γ-H2AX foci) with specific antibodies. The primary fibroblasts, established from FA patients, were exposed to γ-rays, a dose of 2 Gy (60Co), incubated for up to 24 hours under repair-permissive conditions, and assayed for the level of γ-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 γ-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.
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© 2010 Tohoku University Medical Press
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