Phase 4 (resting membrane potential) averages about −90 millivolts.

TLS Online TPP Program

#Id: 3977

#Unit 2. Cellular Organization

The degree of supercoiling of bacterial DNA is maintained by regulation of the net activity of topoisomerases, I and II.

TLS Online TPP Program

#Id: 3980

#Unit 2. Cellular Organization

Eukaryotic cells also have type I and type II topoisomerases. The type I enzymes are topoisomerases I and III;

The eukaryotic type II topoisomerases cannot underwind DNA (introduce negative supercoils), but they can relax both positive and negative supercoils.

TLS Online TPP Program

#Id: 3981

#Unit 2. Cellular Organization

The quinolone antibiotics, inhibits bacterial DNA gyrase and topoisomerase IV, as ciprofloxacin (Cipro). The quinolones act by blocking the last step of the topoisomerase reaction, the resealing of the DNA strand breaks. Ciprofloxacin is a wide-spectrum antibiotic.

TLS Online TPP Program

#Id: 3982

#Unit 2. Cellular Organization

Camptothecin is an inhibitor of eukaryotic type I topoisomerases.

Irinotecan (Campto) and topotecan (Hycamtin)—used to treat colorectal cancer and ovarian cancer.

All these drug's act by trapping the topoisomerase-DNA complex in which the DNA is cleaved, inhibiting religation.

TLS Online TPP Program

#Id: 3983

#Unit 2. Cellular Organization

The human type II topoisomerases are targeted by doxorubicin (Adriamycin), etoposide (Etopophos), and ellipticine.

Most of these drugs stabilize the covalent topoisomerase-DNA (cleaved) complex.

TLS Online TPP Program

#Id: 3985

#Unit 2. Cellular Organization

Gyrases are A2B2 heterotetramers in which the B subunits bind and hydrolyze ATP and the A subunits mediate the double-strand cleavage, strand passage, and reunion reactions.

The eukaryotic type II topoisomerases are homologous to gyrases but with their A and B subunits fused so that they are homodimers.