# Molecular Consequences of Myotonic Dystrophy Type 2-causing CCTG DNA Repeats

> **NIH NIH R15** · CALIFORNIA STATE UNIVERSITY SAN MARCOS · 2024 · $434,750

## Abstract

Project Summary
Myotonic dystrophy type 2 is a genetic disorder characterized by progressive muscle wasting and
weakness that is caused by long CCTG DNA repeats. Individuals can have up to 11,000 CCTG repeats
within the CNBP gene responsible for disease. The proposed project will elucidate the molecular
mechanisms of CCTG repeat instability with a specific focus on large-scale contractions and DNA
breakage using budding yeast S. cerevisiae as a model organism. Understanding the molecular
mechanisms of contractions is important to evaluate whether manipulating this process would be a
viable approach to treat repeat expansion disease. We will evaluate the role of genes involved in the
mismatch repair pathway on large-scale contractions. We will carry out genetic analysis of double
mutants and specific point mutants that are candidates for study because of their role in protein binding
domains or implications from human genome wide association studies. Recently, my lab showed that
disease-associated lengths of CCTG repeats cause chromosomal fragility in vivo. This project will
elucidate how variables such as genomic location and DNA replication dynamics affect CCTG DNA
fragility, which has important implications for understanding the mechanisms of expansions and
chromosomal translocations. Finally, we will investigate CCTG repeat-associated gene expression from
a distinct angle by characterizing differential effects of repeat length and orientation on steady-state
transcript levels and RNA splicing. Altogether, the proposed studies will provide fundamental insights
into the molecular mechanisms of DNA replication, repair, and transcription that underlie the etiology of
the tetranucleotide expansion disease DM2.

## Key facts

- **NIH application ID:** 10975184
- **Project number:** 1R15GM155842-01
- **Recipient organization:** CALIFORNIA STATE UNIVERSITY SAN MARCOS
- **Principal Investigator:** Jane C Kim
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $434,750
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975184

## Citation

> US National Institutes of Health, RePORTER application 10975184, Molecular Consequences of Myotonic Dystrophy Type 2-causing CCTG DNA Repeats (1R15GM155842-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10975184. Licensed CC0.

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