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

PMID:19390626

From GONUTS
Jump to: navigation, search
Citation

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

Abstract

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.

Links

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

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TOP2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q53H47

F

Seeded From UniProt

complete

HUMAN:SETMR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11388

F

Seeded From UniProt

complete

HUMAN:SETMR

involved_in

GO:0071157: negative regulation of cell cycle arrest

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.