# The role of O-GlcNAcylation in DNA damage repair and cancer therapy

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $395,738

## Abstract

Project Summary/Abstract
 O-linked N-acetyglucosaminylation (O-GlcNAcylation) is a reversible posttranslational modification that
plays a key role in ionizing radiation (IR)-induced DNA damage response. O-GlcNAcylation is catalyzed by O-
GlcNActransferase (OGT), which transfers N-acetyl-D-glucosamine from UDP-GlcNAc to serine or threonine
residues of proteins. This posttranslational modification is also removed by O-GlcNAcase (OGA). In our
studies, we have shown that O-GlcNAcylation is significantly enriched at DNA lesions. Since the acceptors of
O-GlcNAcylation are serine or threonine residues, O-GlcNAcylation competes with DNA damage-induced
phosphorylation, which in turn regulates DNA damage repair. Thus, we hypothesize that O-GlcNAcylation is a
key molecular event in response to IR treatment, and targeting O-GlcNAcylation can be an effective
therapeutic strategy to cancer treatment.
 In this research proposal, we plan to focus on one major O-GlcNAcylation substrate MDC1, and examine
the role of O-GlcNAcylated MDC1 in DNA damage response including the phosphorylation events on MDC1,
MDC1 governed protein ubiquitination cascade, and DNA double-strand break repair. Using O-GlcNAcylated
MDC1 as the readouts, we will analyze the biological functions of both OGT and OGA in IR-induced DNA
damage repair, and explore the inhibition of OGA as a novel therapeutic strategy to treat BRCA1 or BRCA2-
deficient tumors in vivo.

## Key facts

- **NIH application ID:** 9933871
- **Project number:** 5R01CA240392-02
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Jeremy Michael Stark
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,738
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933871

## Citation

> US National Institutes of Health, RePORTER application 9933871, The role of O-GlcNAcylation in DNA damage repair and cancer therapy (5R01CA240392-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9933871. Licensed CC0.

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