Taking a Bad Turn: Compromised DNA Damage Response in Leukemia
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-05-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/6/2/11 |
| _version_ | 1827840957778755584 |
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| author | Nadine Nilles Birthe Fahrenkrog |
| author_facet | Nadine Nilles Birthe Fahrenkrog |
| author_sort | Nadine Nilles |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T07:44:40Z |
| format | Article |
| id | doaj.art-17cf72410b064edd84696cb734041b5b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:44:40Z |
| publishDate | 2017-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-17cf72410b064edd84696cb734041b5b2023-09-02T21:02:57ZengMDPI AGCells2073-44092017-05-01621110.3390/cells6020011cells6020011Taking a Bad Turn: Compromised DNA Damage Response in LeukemiaNadine Nilles0Birthe Fahrenkrog1Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, 6041 Charleroi, BelgiumInstitute for Molecular Biology and Medicine, Université Libre de Bruxelles, 6041 Charleroi, BelgiumGenomic 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.http://www.mdpi.com/2073-4409/6/2/11DNA damage responseleukemiadouble-strand break repairnon-homologous end joininghomologous recombination |
| spellingShingle | Nadine Nilles Birthe Fahrenkrog Taking a Bad Turn: Compromised DNA Damage Response in Leukemia Cells DNA damage response leukemia double-strand break repair non-homologous end joining homologous recombination |
| title | Taking a Bad Turn: Compromised DNA Damage Response in Leukemia |
| title_full | Taking a Bad Turn: Compromised DNA Damage Response in Leukemia |
| title_fullStr | Taking a Bad Turn: Compromised DNA Damage Response in Leukemia |
| title_full_unstemmed | Taking a Bad Turn: Compromised DNA Damage Response in Leukemia |
| title_short | Taking a Bad Turn: Compromised DNA Damage Response in Leukemia |
| title_sort | taking a bad turn compromised dna damage response in leukemia |
| topic | DNA damage response leukemia double-strand break repair non-homologous end joining homologous recombination |
| url | http://www.mdpi.com/2073-4409/6/2/11 |
| work_keys_str_mv | AT nadinenilles takingabadturncompromiseddnadamageresponseinleukemia AT birthefahrenkrog takingabadturncompromiseddnadamageresponseinleukemia |