Inhibition of DNA helicase, ATPase and DNA-binding activities of E. coli RecQ helicase by chemotherapeutic agents.
RecQ helicases play an essential role in maintaining genetic integrity in all organisms from Escherichia coli to humans. Defects to these enzymes are responsible for three distinct human diseases: Werner syndrome, Bloom syndrome and Rothmund-Thomson syndrome. All three diseases are characterized by a predisposition to cancer due to increased genomic instability. Previous studies on the effects of non-covalent DNA modifications on the catalytic activity of purified Werner and Bloom DNA helicases have shown that both enzymes have similar sensitivity profiles to these DNA-binding agents and are most strongly inhibited by the minor groove binder distamycin A. In this study, we show that the sensitivity profiles of E. coli RecQ to a number of DNA-binding ligands are different to those observed for WRN and Bloom helicases. These observations may give insights into the differences in molecular mechanisms underlying efficient motor function of RecQ helicases.
Zhang
Bo
B
CNRS, UMR 2027, Institut Curie-Section de Recherche, Centre Universitaire, Bâtiment 110, F-91405 Orsay, France.
Zhang
Ai-hua
AH
Chen
Lei
L
Xi
Xu Guang
XG
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004214:Distamycins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D007364:Intercalating Agents / Q000494:pharmacology*; D053484:RecQ Helicases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D059004:Topoisomerase I Inhibitors
D000998:Antiviral Agents; D004214:Distamycins; D004791:Enzyme Inhibitors; D007364:Intercalating Agents; D059004:Topoisomerase I Inhibitors; C030000:stallimycin; D004247:DNA; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D053484:RecQ Helicases