GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com


Jump to: navigation, search


You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor


Wray, J, Williamson, EA, Royce, M, Shaheen, M, Beck, BD, Lee, SH, Nickoloff, JA and Hromas, R (2009) Metnase mediates resistance to topoisomerase II inhibitors in breast cancer cells. PLoS ONE 4:e5323


DNA replication produces tangled, or catenated, chromatids, that must be decatenated prior to mitosis or catastrophic genomic damage will occur. Topoisomerase IIalpha (Topo IIalpha) is the primary decatenating enzyme. Cells monitor catenation status and activate decatenation checkpoints when decatenation is incomplete, which occurs when Topo IIalpha is inhibited by chemotherapy agents such as the anthracyclines and epididophyllotoxins. We recently demonstrated that the DNA repair component Metnase (also called SETMAR) enhances Topo IIalpha-mediated decatenation, and hypothesized that Metnase could mediate resistance to Topo IIalpha inhibitors. Here we show that Metnase interacts with Topo IIalpha in breast cancer cells, and that reducing Metnase expression significantly increases metaphase decatenation checkpoint arrest. Repression of Metnase sensitizes breast cancer cells to Topo IIalpha inhibitors, and directly blocks the inhibitory effect of the anthracycline adriamycin on Topo IIalpha-mediated decatenation in vitro. Thus, Metnase may mediate resistance to Topo IIalpha inhibitors, and could be a biomarker for clinical sensitivity to anthracyclines. Metnase could also become an important target for combination chemotherapy with current Topo IIalpha inhibitors, specifically in anthracycline-resistant breast cancer.


PubMed PMC2669129 Online version:10.1371/journal.pone.0005323


Anthracyclines/pharmacology; Antigens, Neoplasm/metabolism; Breast Neoplasms/enzymology; Breast Neoplasms/metabolism; Cell Line, Tumor; DNA Topoisomerases, Type II/metabolism; DNA-Binding Proteins/antagonists & inhibitors; DNA-Binding Proteins/metabolism; Drug Resistance, Neoplasm; Enzyme Inhibitors/pharmacology; Female; Histone-Lysine N-Methyltransferase/metabolism; Humans; Topoisomerase II Inhibitors