The Effects of Three Single Amino Acid Mutations in the XPD Gene on the Structure and Function of the DNA Helicase It Encodes For, and Their Role in the Development of Preeclampsia

Mackenzie Gladhill and Dr. Joshua Sokoloski, Department of Chemistry, Salisbury University, 1101 Camden Avenue, Salisbury MD 21774

Preeclampsia is a gestational complication that affects 3-8% of pregnant women around the world and is one of the major causes of premature births. The origin of this disorder has been connected to impaired placental attachment and oxidative stress; however, the main cause is not yet known. Recent research has been completed concerning the XPD gene, which encodes a DNA helicase that is a subunit of general transcription factor IIH. This DNA helicase plays a role in the nucleotide excision repair function during DNA replication, as well as RNA-polymerase II-mediated transcription. Certain mutations in the C terminal and helical surfaces of XPD were found to affect the binding of XPD helicase to other subunits of transcription factor IIH, which can lead to abnormal placental development, oxidative stress, and ultimately hypertension and proteinuria; the main characteristics of preeclampsia. In order to further determine which mutations in XPD can lead to preeclampsia, I studied the effect of three single amino acid mutations on the structure and function of XPD helicase. The L461V, D681W and A725P mutations were predicted to have a destabilizing effect on the structure of the helicase enzyme due to their placements in the secondary structure, which likely alters the tertiary structure of the protein and effects the helicase and DNA repair functions of the XPD protein by interfering with its binding to general transcription factor IIH. The multifactorial characteristic of preeclampsia creates issues concerning treatment options, with the only known cure for the disorder being premature delivery of the fetus. Knowledge of known XPD mutations can provide sites for gene therapy, providing preventative measures to preeclampsia that would be beneficial to the public; especially now with the increasing spread of COVID-19 which has been shown to increase the severity of the gestational complication. 

Additional Abstract Information

Presenter: Mackenzie Gladhill

Institution: Salisbury University

Type: Poster

Subject: Biochemistry

Status: Approved

Time and Location

Session: Poster 2
Date/Time: Mon 3:00pm-4:00pm
Session Number: 2501