# Project 4: Coordinating Nucleolytic Pathways During Crosslink Repair

> **NIH NIH P01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $348,609

## Abstract

PROJECT SUMMARY
Interstrand crosslinks (ICLs) are the most toxic lesions in the cell and are known to be effective in cancer
treatment. Understanding how ICLs are repaired in cancers will allow us to take advantage of these agents for
cancer treatment, to avoid therapy resistance, and to develop biomarkers that can be used to prevent
overtreatment for patients who are not responding to these agents. However, despite extensive studies in this
area, it remains challenging to come up with a detailed hypothesis and reveal precisely how multiple DNA
repair enzymes and pathways act together in ICL repair. This Program Project brings together experts in
various aspects of DNA repair pathways and aims at addressing this difficult question. Project 4 focuses on a
critical scaffold protein SLX4. Aim 1 of this project will determine the mechanisms underlying the cell cycle-
dependent regulation of SLX4-containing protein complexes and investigate how SLX4 and MSH2 complexes
act together to promote ICL repair. Aim 2 will define mechanistically how SLX4 and SLX4IP are recruited to
DNA damage sites and participate in ICL repair. Aim 3 attempts to uncover the connection between SLX4
complex and FA pathway in ICL repair and further determine the significance of these repair components in
cancer therapy. These studies, together with the ones proposed in Projects 1-3, will provide a framework of
ICL repair in humans.

## Key facts

- **NIH application ID:** 10129300
- **Project number:** 5P01CA193124-05
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Junjie Chen
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $348,609
- **Award type:** 5
- **Project period:** 2017-02-10 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129300

## Citation

> US National Institutes of Health, RePORTER application 10129300, Project 4: Coordinating Nucleolytic Pathways During Crosslink Repair (5P01CA193124-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129300. Licensed CC0.

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