Nature Communications (Dec 2019)
Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death
- Jerry H. Houl,
- Zu Ye,
- Chris A. Brosey,
- Lakshitha P. F. Balapiti-Modarage,
- Sarita Namjoshi,
- Albino Bacolla,
- Daniel Laverty,
- Brian L. Walker,
- Yasin Pourfarjam,
- Leslie S. Warden,
- Naga Babu Chinnam,
- Davide Moiani,
- Roderick A. Stegeman,
- Mei-Kuang Chen,
- Mien-Chie Hung,
- Zachary D. Nagel,
- Tom Ellenberger,
- In-Kwon Kim,
- Darin E. Jones,
- Zamal Ahmed,
- John A. Tainer
Affiliations
- Jerry H. Houl
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Zu Ye
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Chris A. Brosey
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Lakshitha P. F. Balapiti-Modarage
- Department of Chemistry, The University of Arkansas at Little Rock
- Sarita Namjoshi
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Albino Bacolla
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Daniel Laverty
- Harvard University, School of Public Health
- Brian L. Walker
- Department of Chemistry, The University of Arkansas at Little Rock
- Yasin Pourfarjam
- Department of Chemistry, University of Cincinnati
- Leslie S. Warden
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Naga Babu Chinnam
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Davide Moiani
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Roderick A. Stegeman
- Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine
- Mei-Kuang Chen
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Mien-Chie Hung
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- Zachary D. Nagel
- Harvard University, School of Public Health
- Tom Ellenberger
- Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine
- In-Kwon Kim
- Department of Chemistry, University of Cincinnati
- Darin E. Jones
- Department of Chemistry, The University of Arkansas at Little Rock
- Zamal Ahmed
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- John A. Tainer
- Departments of Cancer Biology and of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center
- DOI
- https://doi.org/10.1038/s41467-019-13508-4
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 15
Abstract
PARG catalyzes the removal of poly(ADP-ribose) (PAR) from target proteins and executes critical functions in the DNA damage response. Here the authors provide structural and biological insight with small molecule PARG inhibitors and show that PARG inhibition sensitizes cells to ionizing radiation and kills cancer cells through replication fork defects.
