Intercalating TOP2 Poisons Attenuate Topoisomerase Action at Higher Concentrations
نویسندگان
چکیده
منابع مشابه
Targeting of Chk2 as a countermeasure to dose-limiting toxicity triggered by topoisomerase-II (TOP2) poisons
The DNA damage response (DDR) gene cell cycle checkpoint kinase 2 (Chk2) triggers programmed cell death and lethal radiation-induced toxicity in mice in vivo. However, it is not well established to what extent targeting of Chk2 may protect from dose-limiting toxicities (DLT) inflicted by mainstay cancer chemotherapy. We screened different classes of chemotherapy in wild type and Chk2-deficient ...
متن کاملSUMO-Targeted DNA Translocase Rrp2 Protects the Genome from Top2-Induced DNA Damage.
The action of DNA topoisomerase II (Top2) creates transient DNA breaks that are normally concealed inside Top2-DNA covalent complexes. Top2 poisons, including ubiquitously present natural compounds and clinically used anti-cancer drugs, trap Top2-DNA complexes. Here, we show that cells actively prevent Top2 degradation to avoid the exposure of concealed DNA breaks. A genome-wide screen revealed...
متن کاملTwo new flavonol glycosides as DNA topoisomerase I poisons.
Flavonoids are secondary plant metabolites whose anticancer properties are actually being studied from an epidemiological and pharmacological point of view. They are believed to be implicated in the lower risk of some forms of cancer observed in Asian countries, due to their capacity to control cell proliferation, to act on certain regulatory enzymes as protein kinases or topoisomerases. Based ...
متن کاملRoles of nonhomologous end-joining pathways in surviving topoisomerase II-mediated DNA damage.
Topoisomerase II is a target for clinically active anticancer drugs. Drugs targeting these enzymes act by preventing the religation of enzyme-DNA covalent complexes leading to protein-DNA adducts that include single- and double-strand breaks. In mammalian cells, nonhomologous repair pathways are critical for repairing topoisomerase II-mediated DNA damage. Because topoisomerase II-targeting agen...
متن کاملCyclometalated platinum(II) complexes as topoisomerase IIα poisons.
A platinum(II)-based major groove binder [Pt(II)(C^N)(C≡NR)(2)](+) (HC^N = 2-phenylpyridine (phpy), R = 2-naphthyl) was identified as a potent human topoisomerase IIα poison. It stabilizes the covalent TopoIIα-DNA cleavage complex and induces cancer cell death with potency significantly higher than the widely clinically used TopoIIα poison Vp-16.
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Molecular Pharmacology
سال: 2019
ISSN: 0026-895X,1521-0111
DOI: 10.1124/mol.119.117259