Biopolymers and Cell. 2011; 27(5): 398-403
TREATMENT OF LYMPHOID CELLS WITH THE TOPOISOMERASE II POISON ETOPOSIDE LEADS TO AN INCREASED JUXTAPOSITION OF AML1 AND ETO GENES ON THE SURFACE OF NUCLEOLI
1Rubtsov M. A., 1Glukhov S. I., 3Allinne J., 3Pichugin A., 3Vassetzky Y. S., 1,2Razin S. V., 2Iarovaia O. V.
1Moscow State University
1/12, Leninskie Gory, Moscow, Russian Federation, 119899
2 Institute of Gene Biology, RAS
34/5, Vavilov Str., Moscow, Russia Federation, 119334
3 CNRS UMR 8126, University Paris-Sud 11, IGR
39, Camille-Desmoulins Str., 94805 Villejuif, France
AML1 and ETO genes are known partners in the t(8,21) translocation associated with the treatment-related leukaemias in the patients receiving chemotherapy with DNA-topoisomerase II (topo II) poisons. Aim. To determine whether the genes AML1 and ETO are in close proximity either permanently or temporarily in the nucleus. Methods. 3D FISH. Results. We found that in 5 % of untreated cells, alleles of AML1 and ETO are in close proximity. This number increased two-fold in the cells treated with the topo II poison etoposide. Surprisingly, in more than 50 % of the cases observed, co-localization of the genes occurred at the nucleoli surface. We found also that the treatment of cells triggers preferential loading of RAD51 onto bcr of the AML1 and ETO genes. Conclusions. Our results suggest that the repair of DNA lesions introduced by topoisomerase II poisons may be mediated simultaneously by multiple mechanisms, which may be the cause of mistakes resulting in translocations. |
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