Phosphorylation on multiple sites by G1 CDKs blocks Rb from associating with E2F and promotes its export out of the nucleus.

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.

TLS Online TPP Program

#Id: 3986

#Unit 2. Cellular Organization

Addition of a topoisomerase greatly facilitates nucleosome association with cccDNA.

When a topoisomerase is present during nucleosome assembly, it cannot act on the DNA bound to the nucleosome. Instead, the topoisomerase relaxes the DNA not included in nucleosomes, reducing the positive superhelical density in these regions by decreasing the linking number.

TLS Online TPP Program

#Id: 3988

#Unit 2. Cellular Organization

By maintaining the unbound DNA in a relaxed state, topoisomerases facilitate the binding of histones to the DNA and the formation of additional nucleosomes.

Importantly, the overall effect on the plasmid is that the linking number is decreased as more nucleosomes are assembled

TLS Online TPP Program

#Id: 3990

#Unit 2. Cellular Organization