TY - JOUR
T1 - Fanconi anemia
T2 - Genetic analysis of a human disease using chicken system
AU - Takata, M.
AU - Kitao, H.
AU - Ishiai, M.
N1 - Funding Information:
ACKNOWLEDGMENT Supported in part by National Institutes of Health Grants DK 32018 and DK 31988.
PY - 2007/7
Y1 - 2007/7
N2 - Fanconi anemia (FA) is a rare hereditary disorder characterized by skeletal abnormalities, bone marrow failure, and an increased incidence of cancer. The basic cellular abnormality in FA has been postulated to lie in the DNA repair mechanisms because cells from FA patients display chromosomal breakage, which is particularly remarkable following induction of DNA crosslinks. However, experimental evidence for this hypothesis has been lacking. To test whether DNA repair is really defective in FA cells, we disrupted several FA genes in chicken B cell line DT40. By measuring efficiency of gene conversion and hypermutation at the Immunoglobulin locus, we have shown that DT40 FA mutant cell lines exhibited defects in homologous DNA recombination, and possibly, translesion synthesis. However, levels of sister chromatid exchange, another important cellular event mediated by HR, were not reduced, possibly indicating the role of FA genes only in a subpathway of HR. Our results indicate that chicken DT40 cells could be highly useful in molecular dissection of basic biochemical processes, which are deficient in a human genetic disorder.
AB - Fanconi anemia (FA) is a rare hereditary disorder characterized by skeletal abnormalities, bone marrow failure, and an increased incidence of cancer. The basic cellular abnormality in FA has been postulated to lie in the DNA repair mechanisms because cells from FA patients display chromosomal breakage, which is particularly remarkable following induction of DNA crosslinks. However, experimental evidence for this hypothesis has been lacking. To test whether DNA repair is really defective in FA cells, we disrupted several FA genes in chicken B cell line DT40. By measuring efficiency of gene conversion and hypermutation at the Immunoglobulin locus, we have shown that DT40 FA mutant cell lines exhibited defects in homologous DNA recombination, and possibly, translesion synthesis. However, levels of sister chromatid exchange, another important cellular event mediated by HR, were not reduced, possibly indicating the role of FA genes only in a subpathway of HR. Our results indicate that chicken DT40 cells could be highly useful in molecular dissection of basic biochemical processes, which are deficient in a human genetic disorder.
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U2 - 10.1159/000103197
DO - 10.1159/000103197
M3 - Article
C2 - 17675877
AN - SCOPUS:34547634597
VL - 117
SP - 346
EP - 351
JO - Cytogenetic and Genome Research
JF - Cytogenetic and Genome Research
SN - 1424-8581
IS - 1-4
ER -
