# Identification of a novel tumor suppressorof melanoma and UV-induced genome instability

> **NIH NIH R21** · LOYOLA UNIVERSITY CHICAGO · 2022 · $192,500

## Abstract

Skin cancer is one of the most common cancers in the US and imposes a high economic burden. Most skin
cancers, including malignant melanoma, are caused by ultraviolet (UV) light-induced DNA damage and genome
instability. It is well known that UV radiation (UVR)-induced bulky DNA adducts are barriers for normal replication
progression, and their formation causes replication fork stalling that is a major driving force of genome instability.
Failure to stabilize stalled forks and resume stalled replication often causes fork collapse, generating DNA breaks
and genome instabilities that lead to tumorigenesis. However, the mechanism underlying how genome stability
is maintained and how stalled replication is rescued after UV exposure is poorly understood. Understanding such
mechanism is thus important for understanding early events in melanomagenesis. Moreover, enhancing
replication stress levels in tumor cells may offer a promising cancer therapeutic approach, in particular for treating
cancers harboring mutations in replication stress response genes. Thus, obtaining an in-depth understanding on
replication stress suppression and fork repair may assist in developing novel approaches to facilitate targeted
therapy of melanoma.
 The long-term goal of our research program is to delineate the mechanisms for maintaining genome stability
in response to exposure to environmental genotoxins. PI’s lab has pioneered in identifying the CST complex −
a trimeric protein complex consisting of CTC1, STN1, TEN1 that binds to ssDNA with high affinity – as an
important player in maintaining global genome integrity upon replication perturbation. Our recent data suggest
the potential involvement of CST in suppressing UVR-induced genome instability. The goal of this proposal is to
test the hypothesis that CST plays an important role in regulating replication reinitiation when forks are blocked
by UV-induced bulky DNA adducts. CST dysfunction may elevate UVR-induced genome instability and increase
melanoma formation. In Aim 1, we will determine how CST facilitates DNA synthesis when UV-induced bulky
lesions block replication progression. In Aim 2, we will use a new mouse model to determine whether specific
disruption of STN1 in mature melanocytes promotes UVR-induced melanoma production in vivo. It is expected
that results from the proposed research will offer novel insights into our understanding of genome protection
after UV damage and potentially identify a novel tumor suppressor of melanoma, thus facilitating the
development of new approaches for melanoma therapy.

## Key facts

- **NIH application ID:** 10539561
- **Project number:** 1R21ES034636-01
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Weihang Chai
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $192,500
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10539561

## Citation

> US National Institutes of Health, RePORTER application 10539561, Identification of a novel tumor suppressorof melanoma and UV-induced genome instability (1R21ES034636-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10539561. Licensed CC0.

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