Understanding REV1 inhibition-dependent mechanisms of TNR instability
Conference Year
January 2022
Abstract
Trinucleotide repeats (TNRs) are prone to genomic instability in the form of expansion or contractions. This is especially problematic in specific genes where repeat expansion results in neurodegenerative disorders. Specifically, expanded CAG repeats in the HTT gene cause Huntington’s Disease. Because these repeats are unstable, their mutagenesis can be triggered by various things, including environmental factors. Here, we show that REV1, a key translesion synthesis polymerase, has a protective effect on CAG repeat lengths. When REV1 was inhibited in cells, there was increased CAG repeat instability. Additionally, REV1 inhibitor drugs JH-RE-06.NaOH and Drug 4 have a cryoprotective effect on cells.
Primary Faculty Mentor Name
Nimrat Chatterjee
Graduate Student Mentors
Kanayo Ikeh, Joshua Victor, Erica Lamkin
Faculty/Staff Collaborators
Jamie Deutsch
Student Collaborators
Andrew Crompton, Anthony March
Status
Undergraduate
Student College
College of Agriculture and Life Sciences
Program/Major
Molecular Genetics
Primary Research Category
Biological Sciences
Understanding REV1 inhibition-dependent mechanisms of TNR instability
Trinucleotide repeats (TNRs) are prone to genomic instability in the form of expansion or contractions. This is especially problematic in specific genes where repeat expansion results in neurodegenerative disorders. Specifically, expanded CAG repeats in the HTT gene cause Huntington’s Disease. Because these repeats are unstable, their mutagenesis can be triggered by various things, including environmental factors. Here, we show that REV1, a key translesion synthesis polymerase, has a protective effect on CAG repeat lengths. When REV1 was inhibited in cells, there was increased CAG repeat instability. Additionally, REV1 inhibitor drugs JH-RE-06.NaOH and Drug 4 have a cryoprotective effect on cells.