# Project 2: Characterizing the role of ATM and MSH2 in genome stability

> **NIH NIH U54** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $197,300

## Abstract

Cancer cells have mutations that alter when they will grow and die. The cells acquire these mutations through
DNA damage. Normally, when a cell experiences DNA damage, DNA repair proteins are recruited to correct
the damaged or mutated DNA. If the damage is not corrected, a cell death pathway is activated that kills the
cell. However, mistakes in the DNA damage response can occur, resulting in the survival of cells with mutated
DNA that can give rise to cancer. People who are born with mutations in genes involved in DNA repair are
predisposed to developing cancer and many people not born with these mutations who develop cancer have
been found to have acquired mutations in DNA repair genes in their tumors. To study how cells repair DNA
damage, we use mouse B cells as a model system. To generate antibodies that recognize and eliminate
pathogens, B cells are genetically programmed to mutate and delete antibody coding genes. The B cells
carefully coordinate their DNA damage and DNA repair pathways to avoid triggering a cell death pathway.
ATM (ataxia telangiectasia mutated) and MSH2 (MutS homologue 2) are proteins that are essential for two
distinct DNA repair pathways. Mice engineered to lack either ATM or MSH2 display defects in antibody
production and have a similar cancer predisposition as people born with mutations in these DNA repair genes.
However, mice that lack both ATM and MSH2 are not viable (unpublished data). We hypothesize that the
combined loss of ATM and MSH2 causes the accumulation of genomic DNA damage that prevents mouse
development. We propose experiments to characterize the mechanism by which ATM and MSH2 cooperatively
regulate genome stability and experiments to determine if these unique molecular pathways can be exploited
therapeutically in cancer. The research will be led by Dr. Vuong and Dr. Chaudhuri at The City College of New
York and Memorial Sloan-Kettering Cancer Center, respectively. Dr. Vuong, a former trainee of Dr. Chaudhuri,
will supervise CCNY students in the proposed research, which will enhance the pipeline of underrepresented
minorities trained in cancer research. The completion of the proposed research will improve the
competitiveness of future grant applications from Dr. Vuong, who is a new investigator.

## Key facts

- **NIH application ID:** 10021576
- **Project number:** 5U54CA137788-12
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jayanta Chaudhuri
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,300
- **Award type:** 5
- **Project period:** 2008-09-26 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021576

## Citation

> US National Institutes of Health, RePORTER application 10021576, Project 2: Characterizing the role of ATM and MSH2 in genome stability (5U54CA137788-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10021576. Licensed CC0.

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