Tomasz Poplawski
Professor @ University of Lodz
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BCR/ABL downregulates DNA-PK(CS)-dependent and upregulates backup non-homologous end joining in leukemic cells
Publications
Year
2010
Type(s)
Journal Article
Author(s)
Poplawski, Tomasz and Blasiak, Janusz
Source
Molecular Biology Reports, 37(5): 2309—2315, 2010
BibTeX
BibTeX
BibTeX
@article{poplawski_bcr/abl_2010, title = {{BCR}/{ABL} downregulates {DNA}-{PK}({CS})-dependent and upregulates backup non-homologous end joining in leukemic cells}, volume = {37}, issn = {1573-4978}, doi = {10.1007/s11033-009-9730-0}, abstract = {Non-homologous end joining (NHEJ) and homologous recombination repair (HRR) are the main mechanisms involved in the processing of DNA double strand breaks (DSBs) in humans. We showed previously that the oncogenic tyrosine kinase BCR/ABL stimulated DSBs repair by HRR. To evaluate the role of BCR/ABL in DSBs repair by NHEJ we examined the ability of leukemic BCR/ABL-expressing cell line BV173 to repair DNA damage induced by two DNA topoisomerase II inhibitors: etoposide and sobuzoxane. DNA lesions induced by sobuzoxane are repaired by a NHEJ pathway which is dependent on the catalytic subunit of protein kinase dependent on DNA (DNA-PK(CS); D-NHEJ), whereas damage evoked by etoposide are repaired by two distinct NHEJ pathways, dependent on or independent of DNA-PK(CS) (backup NHEJ, B-NHEJ). Cells incubated with STI571, a highly specific inhibitor of BCR/ABL, displayed resistance to these agents associated with an accelerated kinetics of DSBs repair, as measured by the neutral comet assay and pulsed field gel electrophoresis. However, in a functional NHEJ assay, cells preincubated with STI571 repaired DSBs induced by a restriction enzyme with a lower efficacy than without the preincubation and addition of wortmannin, a specific inhibitor of DNA-PK(CS), did not change efficacy of the NHEJ reaction. We suggest that BCR/ABL switch on B-NHEJ which is more error-prone then D-NHEJ and in such manner contribute to the increase of the genomic instability of leukemic cells.}, language = {eng}, number = {5}, journal = {Molecular Biology Reports}, author = {Poplawski, Tomasz and Blasiak, Janusz}, month = jun, year = {2010}, pmid = {19697154}, keywords = {Humans, DNA Repair, Cell Line, Tumor, Leukemia, Nuclear Proteins, Recombination, Genetic, Cell Survival, Time Factors, Fusion Proteins, bcr-abl, Piperazines, DNA-Activated Protein Kinase, Androstadienes, DNA Breaks, Double-Stranded, Down-Regulation, Etoposide, Up-Regulation, comet assay}, pages = {2309--2315}