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020 ▼a 9781085732963
035 ▼a (MiAaPQ)AAI13895833
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 574
1001 ▼a Burleigh, Katelyn.
24510 ▼a Human DNA-PK Activates a STING-independent DNA Sensing Pathway.
260 ▼a [S.l.]: ▼b University of Washington., ▼c 2019.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2019.
300 ▼a 65 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
500 ▼a Advisor: Stetson, Daniel B.
5021 ▼a Thesis (Ph.D.)--University of Washington, 2019.
506 ▼a This item must not be sold to any third party vendors.
506 ▼a This item must not be added to any third party search indexes.
520 ▼a Recognition of foreign nucleic acids is critical for antiviral defense. Detection of DNA is mediated by the cGAS-STING pathway, which activates a potent type I interferon response. This pathway is broadly required for antiviral defense across cell types and species, and its relevance in context of infection, cancer, and autoimmunity has been thoroughly established. However, we have discovered an additional STING-independent DNA sensing pathway (SIDSP) in human cells. Using STING KO human cell lines, we find that the induction of interferon is indeed abrogated at early timepoints, but surprisingly, at later timepoints, we observe a robust DNA-induced interferon response. Here we identify DNA-PK as the sensor for the SIDSP and demonstrate that its kinase activity is required for the antiviral response. We show that a heat shock protein HSPA8/HSC70 is phosphorylated after DNA stimulation and acts as a marker for the SIDSP. Finally, we explore how DNA viruses antagonize both the cGAS-STING pathway and the SIDSP. Our work highlights the importance of nucleic acid sensing for both host and virus and has implications for modulating DNA sensing in order to improve therapies for cancer or autoimmunity.
590 ▼a School code: 0250.
650 4 ▼a Immunology.
650 4 ▼a Cellular biology.
690 ▼a 0982
690 ▼a 0379
71020 ▼a University of Washington. ▼b Molecular and Cellular Biology.
7730 ▼t Dissertations Abstracts International ▼g 81-03B.
773 ▼t Dissertation Abstract International
790 ▼a 0250
791 ▼a Ph.D.
792 ▼a 2019
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15491649 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1008102
991 ▼a E-BOOK