| |
| author |
Uma Kantheti
| | title |
The Interferon Response to Exogenous DNA and DNA Damage is Dependent on DNA-PK along with cGAS/STING Pathway
| | abstract |
Two pattern recognition receptors (PRRs) known as interferon-inducible protein
16 (IFI16) and cyclic GMP-AMP synthase (cGAS) bind to viral DNA and to an adaptor
protein found on the endoplasmic reticulum called STING. This results in downstream
signaling to produce interferon. However, it is not clear whether other classes of DNA-
binding proteins, such as DNA damage kinases, also participate in the interferon response
to viral infections. Additionally, it is unknown whether DNA-sensing PRRs like IFI16
and cGAS play a role in responding to damaged host DNA. In this study we show, by
comparing interferon responses to exogenous nucleic acid in cells that were treated with a
DNA-PK inhibitor and in untreated cells, that a DNA damage kinase known as DNA-
dependent protein kinase (DNA-PK) is involved in PRR signaling. DNA-PK was shown
to physically associate with IFI16 and STING. Additionally, we investigated the
possibility of phosphorylation of cGAS, STING, and/or IFI16 by DNA-PK through
bioinformatics using a protein database known as ScanSite 4.0. In order to see PRRs' role
in DNA damage, treating IFI16 knockout cell lines with DNA damage agents resulted in
a decreased type I IFN response to DNA damage. These findings show DNA repair
proteins such as DNA-PK playing a role in mediating an interferon response to viral
infections as well as DNA-sensing PRR such as IFI16's role in responding to DNA
damage. These findings have implications in understanding viral pathogenesis and
developing new therapies for viral infections and cancer.
| | school |
The College of Liberal Arts, Drew University
| | degree |
B.A. (2019)
|
| advisor |
Brianne Barker
|
| committee |
Joanna Miller
Kimberly Choquette
|
| full text | UKantheti.pdf - requires Drew uLogin |
| |
