BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cells

Artur Slupianek; Michal O. Nowicki; Mateusz Koptyra; Tomasz Skorski

doi:10.1016/j.dnarep.2005.10.005

BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cells

Artur Slupianek, Michal O. Nowicki, Mateusz Koptyra, Tomasz Skorski

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

The oncogenic BCR/ABL tyrosine kinase facilitates the repair of DNA double-strand breaks (DSBs). We find that after γ-irradiation BCR/ABL-positive leukemia cells accumulate more DSBs in comparison to normal cells. These lesions are efficiently repaired in a time-dependent fashion by BCR/ABL-stimulated non-homologous end-joining (NHEJ) followed by homologous recombination repair (HRR) mechanisms. However, mutations and large deletions were detected in HRR and NHEJ products, respectively, in BCR/ABL-positive leukemia cells. We propose that unfaithful repair of DSBs may contribute to genomic instability in the Philadelphia chromosome-positive leukemias.

Original language	English
Pages (from-to)	243-250
Number of pages	8
Journal	DNA Repair
Volume	5
Issue number	2
DOIs	https://doi.org/10.1016/j.dnarep.2005.10.005
State	Published - Feb 3 2006
Externally published	Yes

Keywords

BCR/ABL
Double-strand breaks
Homologous recombination
Leukemia
Non-homologous end-joining
Unfaithful repair

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10.1016/j.dnarep.2005.10.005

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title = "BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cells",

abstract = "The oncogenic BCR/ABL tyrosine kinase facilitates the repair of DNA double-strand breaks (DSBs). We find that after γ-irradiation BCR/ABL-positive leukemia cells accumulate more DSBs in comparison to normal cells. These lesions are efficiently repaired in a time-dependent fashion by BCR/ABL-stimulated non-homologous end-joining (NHEJ) followed by homologous recombination repair (HRR) mechanisms. However, mutations and large deletions were detected in HRR and NHEJ products, respectively, in BCR/ABL-positive leukemia cells. We propose that unfaithful repair of DSBs may contribute to genomic instability in the Philadelphia chromosome-positive leukemias.",

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AU - Nowicki, Michal O.

AU - Koptyra, Mateusz

AU - Skorski, Tomasz

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BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cells

Abstract

Keywords

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