# Suppression of duplication-mediated genome rearrangements by protein sumoylation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $12,002

## Abstract

Project summary
Genome rearrangements are mutations that cause numerous genetic diseases including
cancer, immune deficiencies and developmental disorders. Genome rearrangements are
caused by defects in DNA replication and repair pathways, as well as the presence of numerous
"at-risk" sequences in the human genome that are prone to mutations. Protein sumoylation is
reversible and involves the opposing actions of two families of enzymes; the E3 ligases that
catalyze the attachment of Small Ubiquitin-like MOdifier (SUMO) to substrates, and the SUMO
specific proteases that remove them. Our genetic study using Saccharomyces cerevisiae has
identified a major role of these enzymes in preventing diverse genome rearrangements, and has
further uncovered a new paradigm in which spontaneous DNA breaks occurred during DNA
replication caused these genome rearrangements. Additionally, results from our proteomic and
biochemical studies have identified the
Mini-Chromosome Maintenance (MCM) complex at the
DNA replication fork as a major target under the regulation of SUMO. Because inherited
mutations of genes in the SUMO pathways cause genome instability syndrome in mammals,
understanding the molecular basis by which protein sumoylation regulates DNA replication will
impact human health for two major reasons: 1) a comprehensive understanding of the genetic
consequences that arise from mutations to the SUMO pathways, with regards to DNA
replication, will impact the development of assays for cancer diagnosis. 2) Identifying the
molecular mechanism by which SUMO regulates DNA replication will lead to the development of
new therapeutic interventions of human disease. Thus, in the proposed studies we will
characterize the genetics and biochemistry of the SUMO pathways in the model organism S.
cerevisiae. We will pursue the following specific aims: First, we will characterize the function of
protein sumoylation during chromosomal DNA replication. Second, we will investigate the role of
SUMO and ubiquitin in regulating DNA replication. And finally, we will study how reversible
sumoylation of the DNA replisome is regulated. The ultimate goal is to understand how SUMO
regulates DNA replication and how cells utilize this pathway to prevent genome
rearrangements.

## Key facts

- **NIH application ID:** 10808698
- **Project number:** 3R01GM116897-09S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** HUILIN ZHOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $12,002
- **Award type:** 3
- **Project period:** 2015-09-30 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808698

## Citation

> US National Institutes of Health, RePORTER application 10808698, Suppression of duplication-mediated genome rearrangements by protein sumoylation (3R01GM116897-09S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10808698. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*