Trinucleotide repeat instability via DNA base excision repair.

DNA Repair (Amst)

Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL, 33199, United States; Biomolecular Sciences Institute, Florida International University, 11200 SW 8th Street, Miami, FL, 33199, United States; Biochemistry Ph.D. Program, Florida International University, 11200 SW 8th Street, Miami, FL, 33199, United States. Electronic address:

Published: September 2020

Trinucleotide repeat (TNR) instability is the cause of over 40 human neurodegenerative diseases and certain types of cancer. TNR instability can result from DNA replication, repair, recombination, and gene transcription. Emerging evidence indicates that DNA base damage and base excision repair (BER) play an active role in regulating somatic TNR instability. These processes may potentially modulate the onset and progression of TNR-related diseases, given that TNRs are hotspots of DNA base damage that are present in mammalian cells with a high frequency. In this review, we discuss the recent advances in our understanding of the molecular mechanisms underlying BER-mediated TNR instability. We initially discuss the roles of the BER pathway and locations of DNA base lesions in TNRs and their interplay with non-B form DNA structures in governing repeat instability. We then discuss how the coordinated activities of BER enzymes can modulate a balance between the removal and addition of TNRs to regulate somatic TNR instability. We further discuss how this balance can be disrupted by the crosstalk between BER and DNA mismatch repair (MMR) machinery resulting in TNR expansion. Finally, we suggest future directions regarding BER-mediated somatic TNR instability and its association with TNR disease prevention and treatment.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586489PMC
http://dx.doi.org/10.1016/j.dnarep.2020.102912DOI Listing

Publication Analysis

Top Keywords

tnr instability
24
dna base
16
somatic tnr
12
trinucleotide repeat
8
instability
8
repeat instability
8
base excision
8
excision repair
8
tnr
8
base damage
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!