Date of Completion
TLS, protein, DNA damage tolerance, protein-protein interactions
Field of Study
Doctor of Philosophy
DNA contains information that must be safeguarded, but also accessed for transcription and replication. To perform replication, cells use the B-family polymerase enzymes Pold and Pole, which are optimized for accuracy, speed, and processivity. Because the molecular basis of these high-performance characteristics causes these polymerases to fail at sites of DNA damage, which would lead to genomic instability and cell death, cells possess other DNA polymerases to perform this function such as the Y-family of polymerases and the B-family member Polz. These specialized polymerases assemble into a protein complex called the Rev1/Polz mutasome to replicate opposite damaged DNA in a process called translesion synthesis (TLS). While able to replicate damaged DNA, the Y-family TLS polymerases exhibit low-fidelity on undamaged DNA and, consequently, must be prevented from replicating DNA under normal circumstances and recruited only when necessary. To this end, posttranslational modifications and a network of protein-protein interactions control the assembly of the Rev1/Polz mutasome and recruitment to sites of DNA damage. This work focuses on the structures and interactions that control this process of assembly and recruitment in addition to studies on inhibition of TLS, which may be a potential anticancer therapy.
Rizzo, Alessandro A., "Assembly and Inhibition of the Rev1/Polz Mutasome" (2019). Doctoral Dissertations. 2215.
Available for download on Sunday, May 06, 2029