DNA Repair--A Double-Edged Sword in the Genomic Stability of Cancer Cells--The Case of Chronic Myeloid Leukemia

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2015 Nov 24

PMID 26593906

Citations 16

Authors

Elzbieta Pawlowska

Janusz Blasiak

Affiliations

Soon will be listed here.

Abstract

Genomic instability is a common feature of cancer cells, which can result from aberrant DNA damage reaction (DDR). We and others showed that the well-known BCR-ABL1 fusion oncogene, the cause of chronic myeloid leukemia, induced an increased production of reactive oxygen species (ROS) and conferred therapeutic drug resistance by suppression of apoptotic signaling, prolonged G2/M arrest and stimulation of several pathways of DNA repair. However, to protect from apoptosis, cancer cells may tolerate some DNA lesions, which may increase genomic instability. Moreover, BCR/ABL1-stimulated DNA repair might be faulty, especially non-homologous end joining in its alternative forms. Normal DNA repair can remove DNA damage and prevent mutations, reducing genome instability, but on the other hand, due to its imprecise nature, it may increase genomic instability by increasing the ratio of mutagenic DNA lesions. The example of BCR-ABL1-expressing cells shows that DNA repair can both increase and decrease genomic instability of cancer cells and understanding the mechanism of the regulation of these opposite effects would be helpful in anticancer strategies.

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