Catalytic inhibition of topoisomerase II in Werner’s syndrome cell lines enhances chromosomal damage induced by X-rays in the G2 phase of cell cycle
Author(s)
Date Issued
2000
Type
Article
Abstract
PURPOSE: To investigate whether catalytic topoisomerase II activity by ICRF187, a compound that interferes with the catalytic cycle of topoisomerase II without causing DNA damage, could result in a modulation of X-ray-induced chromosomal damage in Werner's syndrome (WS) cell lines.
MATERIALS AND METHODS: Two WS (KO375, DJG) and one normal lymphoblastoid cell line (SNW646) were exposed to X-rays, post-treated with ICRF187 and harvested after various recovery times. Cell progression to mitosis was monitored by 5-bromo-2'-deoxyuridine (BrdUrd) and fluorescent immmunodetection to analyse chromosomal damage in homogeneous treated cell populations in the G1, S or G2 phase of the cell cycle.
RESULTS: In WS cell lines, catalytic inhibition of topoisomerase II activity by ICRF187 resulted in potentiation of X-ray- induced chromosomal damage in the G2 phase of the cell cycle. This potentiation was not observed in the G1 or S phases of the cell cycle, neither in WS nor normal cells.
CONCLUSION: These results point out the possibility that Werner's syndrome protein (WRNp) might play a role in a G2 recombinational pathway of double-strand break repair, cooperating with topoisomerase II and thus contributing to maintain genomic integrity.
Additional information
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Citation
Franchitto, A. et al. 2000. Catalytic inhibition of topoisomerase II in Werner’s syndrome cell lines enhances chromosomal damage induced by X-rays in the G2 phase of cell cycle. "International Journal of Radiation Biology" 76(7): 913-922.
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