Date of Award


Degree Type


Degree Name

Master of Science




Dr. Hong Ling

Second Advisor

Dr. David B. Haniford

Third Advisor

Dr. James Choy


The human DNA polymerase lambda (Pol λ) is a recently discovered member of the X-family DNA polymerases that has been shown to be involved in DNA repair and meiotic recombination, where it plays a gap filling role in these two processes. The protein’s primary sequence is organized into an N-terminal BRCAl-C terminai (BRCT) domain, a proline-rich domain and a C-terminus polymerase beta-like (Pol β-like) domain. Studies have shown that the polymerase’s activity is localized at the C-terminus of the protein and that this activity is partially suppressed by the proline-rich domain. Primer extension assays confirmed the inhibitory effects of the proline-rich domain, however, it also showed that the BRCT domain appeared to subdue or compensate for this effect. This assay also revealed that the proline-rich domain by itself did not significantly increase the protein’s fidelity but when combined with the BRCT domain, there was approximately a 10 fold increase in fidelity. DNA binding assays also showed that the proline-rich domain inhibited the C-terminus domain’s ability to bind DNA; however, it was also observed that this negative effect was suppressed or compensated for by the BRCT domain. NMR and CD data analysis confirmed secondary structure predictions that indicated the proline-rich domain to be essentially a disordered region. The NMR experiment further presented substantiation that there was a weak domaindomain interaction between the proline-rich domain and the C-terminus domain, which may play a crucial role in the protein function.



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