Misrepair of radiation-induced DNA double-strand breaks and its relevance for tumorigenesis and cancer treatment (Review)

  • Authors:
    • Kai Rothkamm
    • Markus Lobrich
  • View Affiliations

  • Published online on: August 1, 2002     https://doi.org/10.3892/ijo.21.2.433
  • Pages: 433-440
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Abstract

The faithful repair of DNA double-strand breaks (DSBs) is probably one of the most critical tasks for a cell in order to maintain its genomic integrity since these lesions may lead to chromosome breaks or rearrangements, mutations, cell death or cancer. DSBs can arise spontaneously during normal cellular DNA metabolism or may be induced by exogenous agents such as ionizing radiation. To overcome the danger that emanates from these lesions, eukaryotic cells have evolved specific pathways for processing DSBs by either homology-dependent or non-homologous repair mechanisms. This review focuses on the formation of genomic rearrangements that arise by joining incorrect break ends and on the factors that influence repair fidelity. Recent studies indicate that the probability for a break to be incorrectly rejoined is fairly low when DSBs are spatially separated but increases drastically when multiple breaks coincide. The formation of genomic rearrangements in situations of multiple breaks is mediated by non-homologous end-joining, the predominant DSB repair pathway in mammalian cells. Interestingly, the same pathway is required for efficiently preserving chromosomal integrity in situations of separated breaks. Furthermore, the probability for a DSB to be faithfully repaired depends on its genomic location and on the cell cycle position. Methods for assaying DSB repair are discussed, again with emphasis on experimental systems that allow to determine whether a DSB is correctly or incorrectly rejoined.

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August 2002
Volume 21 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Rothkamm K and Lobrich M: Misrepair of radiation-induced DNA double-strand breaks and its relevance for tumorigenesis and cancer treatment (Review). Int J Oncol 21: 433-440, 2002.
APA
Rothkamm, K., & Lobrich, M. (2002). Misrepair of radiation-induced DNA double-strand breaks and its relevance for tumorigenesis and cancer treatment (Review). International Journal of Oncology, 21, 433-440. https://doi.org/10.3892/ijo.21.2.433
MLA
Rothkamm, K., Lobrich, M."Misrepair of radiation-induced DNA double-strand breaks and its relevance for tumorigenesis and cancer treatment (Review)". International Journal of Oncology 21.2 (2002): 433-440.
Chicago
Rothkamm, K., Lobrich, M."Misrepair of radiation-induced DNA double-strand breaks and its relevance for tumorigenesis and cancer treatment (Review)". International Journal of Oncology 21, no. 2 (2002): 433-440. https://doi.org/10.3892/ijo.21.2.433