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Functional Analysis Of Cdc45 In The Replication Fork And In Response To Replicative Stress, Amanda Debrot

All ETDs from UAB

DNA replication is a highly conserved and tightly regulated process, with a variety of factors acting to ensure faithful duplication and stability of chromosomal DNA. During replication, positive supercoils form ahead of the advancing replication fork. DNA topoisomerase 1 (Top1) acts to prevent DNA damage by relieving the torsional strain created by these supercoils. The camptothecin (CPT) class of chemotherapeutics target Top1, creating a long-lived DNA-Top1-CPT covalent complex, which leads to S-phase specific DNA lesions and cellular death. Our lab previously performed a genetic screen to isolate mutant proteins that enhance cell sensitivity to Top1-mediated DNA damage. One of the …