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Cells 2017, 6(2), 11; doi:10.3390/cells6020011

Taking a Bad Turn: Compromised DNA Damage Response in Leukemia

Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, 6041 Charleroi, Belgium
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Academic Editor: Prakash Hande
Received: 1 March 2017 / Revised: 7 April 2017 / Accepted: 25 April 2017 / Published: 4 May 2017
(This article belongs to the Special Issue DNA Repair Defects and Telomere Dysfunction in Diseases)
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Abstract

Genomic integrity is of outmost importance for the survival at the cellular and the organismal level and key to human health. To ensure the integrity of their DNA, cells have evolved maintenance programs collectively known as the DNA damage response. Particularly challenging for genome integrity are DNA double-strand breaks (DSB) and defects in their repair are often associated with human disease, including leukemia. Defective DSB repair may not only be disease-causing, but further contribute to poor treatment outcome and poor prognosis in leukemia. Here, we review current insight into altered DSB repair mechanisms identified in leukemia. While DSB repair is somewhat compromised in all leukemic subtypes, certain key players of DSB repair are particularly targeted: DNA-dependent protein kinase (DNA-PK) and Ku70/80 in the non-homologous end-joining pathway, as well as Rad51 and breast cancer 1/2 (BRCA1/2), key players in homologous recombination. Defects in leukemia-related DSB repair may not only arise from dysfunctional repair components, but also indirectly from mutations in key regulators of gene expression and/or chromatin structure, such as p53, the Kirsten ras oncogene (K-RAS), and isocitrate dehydrogenase 1 and 2 (IDH1/2). A detailed understanding of the basis for defective DNA damage response (DDR) mechanisms for each leukemia subtype may allow to further develop new treatment methods to improve treatment outcome and prognosis for patients. View Full-Text
Keywords: DNA damage response; leukemia; double-strand break repair; non-homologous end joining; homologous recombination DNA damage response; leukemia; double-strand break repair; non-homologous end joining; homologous recombination
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Nilles, N.; Fahrenkrog, B. Taking a Bad Turn: Compromised DNA Damage Response in Leukemia. Cells 2017, 6, 11.

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