ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer
Abstract
Platinum resistance remains as a major issue in the therapy for many types of cancer. However, the mechanisms of resistance have not been fully elucidated. ACTL6A gene is frequently amplified in several types of cancer such as lung squamous cell carcinoma, ovarian cancer, and esophageal cancer. ACTL6A is a subunit shared by multiple complexes, including SWI/SNF, INO80, and NuA4/TIP60. We unveil a new role for ACTL6A in repairing cisplatin-induced DNA damage, providing a novel mechanism for cisplatin resistance. We also show that the action of ACTL6A in the repair of cisplatin-induced DNA lesions is through the SWI/SNF remodeling complex. Furthermore, we demonstrate that an HDAC inhibitor can abolish cisplatin resistance caused by ACTL6A overexpression.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 06, 2021
- Source ID
- 10.1073/pnas.2015808118
Entities
People
- Fang-Tsyr Lin
- Weei-Chin Lin
- Yang Xiao
Organizations
- Baylor College of Medicine
- National Cancer Institute
- Rivkin Center for Ovarian Cancer
- United States Department of Defense