Understanding REV1 inhibition-dependent mechanisms of TNR instability

Presenter's Name(s)

Lindsay P. AllenFollow

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

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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.