Writing Resources
Requires the action of many molecular players that need to exert their functions in a perfectly concerted manner For DNA replication to be accurately completed the replication fork must frequently overcome a multitude of structurally unrelated obstacles such as DNA lesions transcribing RNA polymerases and tightly bound protein DNA complexes Stalling of the replication machinery during S phase creates a hazardous situation for cells initiating a subsequent replication fork collapse resulting in genomic instability such as copy number variation Arlt 2011 1 micronuclei formation Xu 2011 2 and loss of heterozygosity Donahue 2006 3 thus contributing to tumorigenesis Kawabata 2011 4 Camptothecin CPT and its derivatives that have been used in anticancer therapy for more than fifteen years are highly selective inhibitors of topoisomerase I TopI that lock the enzyme on DNA during the intermediate step of enzymatic cleavage
