RNA polymerase II (pol II) recognizes many obstacles during transcription elongation, including DNA damage lesions and modifications, via specific interactions and leads to distinct transcriptional outcomes. We investigate three specific types of modifications/lesions in DNA and how they affect the pol II transcription process: 1) unnatural synthetic nucleotides (dNaM and dTPT3), 2) regioisomeric alkylated thymidine lesions (O2-, N3-, O4-EtdT), and 3) non-covalent minor groove DNA binders pyrrole-imidazole (Py-Im) polyamides. In Chapter 1, we investigate pol II transcription and elongation in the presence of synthetic nucleotides (dNaM and dTPT3), and the ability of pol II to distinguish between natural NTPs and the unnatural triphosphates. Selective incorporation of rNaM by pol II only occurs when dTPT3 is in the template strand, and loses its selectivity when dNaM is in the template. In Chapter 2, we discovered distinct patterns of pol II transcriptional bypass for each of the alkylated thymidine lesions. We found that pol II bypass of O2-EtdT is essentially error free, bypass of O4-EtdT is efficient and highly error prone, and bypass of N3-EtdT is extremely slow. In Chapter 3, we found that Py-Im polyamides bound to the minor groove at sequence specific sites causes prolonged pol II arrest upstream of the binding site, due to two specific residues in the pol II Switch 1 region that contribute to the early detection of the obstruction in the minor groove. Taken together, these studies highlight the importance of pol II recognition of DNA damage and modifications in the maintenance of transcriptional fidelity.

In the late nineteenth and early twentieth centuries, the United States experienced a remarkable growth of the immigrant population and witnessed scientific and medical developments that facilitated the selection of desirable and respectable immigrants. Between the 1890s and the 1920s, the American government passed several immigration acts to exclude newcomers with mental or physical defects and expanded the excludable classes of immigrants. The actual number of deportees was small, but their presence alerted the American public of the danger of the "new" immigrants. Compared to physical defects, insanity was difficult to detect due to its relative invisibility and cultural differences in its manifestations and diagnoses. Nevertheless, insanity was often discussed to prove the undesirable nature of the immigrant population, and the popular eugenic ideas of the time period justified its exclusion. Financial concerns at the American borders also posed a problem in detecting immigrants with mental defects. In 1912, against the criticism that immigration officials failed to implement the immigration acts, the Acting Secretary of the Department of Immigration asserted: "A dollar will only go so far, and we cannot get two dollars worth of work for one dollar." The medical deportation of the "alien" insane was not just a political measure against diseased immigrants; it reflected social anxieties of the time period, and the causes and symptoms of insanity among immigrants revealed deeply ingrained gender and racial stereotypes of the "strangers in the land."

Previous research has shown that developing second language (L2) academic writers use a limited set of reporting verbs in comparison to more advanced writers (Biber & Reppen, 1998; Hinkel, 2003; Kwon, Staples, & Partridge, 2018; Neff et al., 2003; Staples & Reppen, 2016). These writers also tend to rely on verbs that are typical for conversation (Biber et al., 1999). The present study examines the effects of corpus-informed instruction on developing L2 writers’ learning of reporting verbs in a first-year writing course by comparing drafts of literature reviews before and after a workshop. The forty-five-minute workshop was designed to improve L2 writers’ lexical and functional uses of reporting verbs using corpus-informed materials. The researchers compared the literature review drafts written by 40 students who participated in the workshop to 38 randomly chosen drafts from our corpus. The results show an increase in the experimental groups’ reporting verb lexical variety and a decrease in the use of verb types used in speech in favor of types used in academic writing. The results suggest that corpus-informed instruction may support L2 writers in the development of lexical and functional reporting verb use.

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