2006
DOI: 10.1093/mutage/gel002
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The repair of gamma-radiation-induced DNA damage is inhibited by microcystin-LR, the PP1 and PP2A phosphatase inhibitor

Abstract: The genotoxic activity of microcystin-LR (MC-LR) is a matter of debate. MC-LR is known to be a phosphatase inhibitor and it may be expected that it is involved in the regulation of the activity of DNA-dependent protein kinase (DNA-PK), the key enzyme involved in the repair of radiation-induced DNA damage. We studied the effect of MC-LR on the repair capacity of radiation-induced DNA damage in human lymphocytes and human glioblastoma cell lines MO59J and MO59K. A dose of 0.5 microg/ml of MC-LR was chosen becaus… Show more

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Cited by 49 publications
(34 citation statements)
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“…However, consistent with the idea that protein phosphatases are not just negative regulators of DNA repair signaling, selective inhibition of PP2A activity impairs DNA repair (7)(8)(9). PP2A function is also essential for activation of cell-cycle checkpoints in response to irradiation (10,11).…”
Section: Introductionmentioning
confidence: 59%
“…However, consistent with the idea that protein phosphatases are not just negative regulators of DNA repair signaling, selective inhibition of PP2A activity impairs DNA repair (7)(8)(9). PP2A function is also essential for activation of cell-cycle checkpoints in response to irradiation (10,11).…”
Section: Introductionmentioning
confidence: 59%
“…The experiments were performed with freshly drawn human G 0 phase lymphocytes (Kaczmarek et al, 1987), which are known to utilize the NHEJ pathway for the repair of DSBs in DNA, supposedly the main lesions, detected by the neutral CA. NHEJ is a relatively fast process, which is completed within 2h after the exposure (Lankoff et al, 2006;Palyvoda et al, 2003). This was also confirmed by kinetics, utilizing the comet test in our laboratory (data not shown).…”
Section: Discussionmentioning
confidence: 99%
“…Douglas et al [49] reported that MC-LR may be implicated in the regulation of the activity of DNA-dependent protein kinase (DNA-PK), which is required for DNA double strand break repair by the process of non-homologous end joining (NHEJ). Subsequently, Lankoff et al [97,98] found that MC-LR inhibited the repair of γ radiation-induced damage and enhanced frequencies of chromosomal aberrations including dicentric chromosomes in human lymphocytes. Moreover, pre-treatment with MC-LR resulted in reduced numbers of γ-H2AX foci in irradiated cells.…”
Section: Genotoxicitymentioning
confidence: 99%