And-1 coordinates with polymerase δ to regulate nucleotide excision repair and UVB-induced skin tumorigenesis

Authors

• Shuyan Zhou, Department of Biochemistry and Molecular Medicine, George Washington University School of Medicine and Health Sciences, GW Cancer Center, Washington, DC, USA.
• Yi Zhang, Department of Biochemistry and Molecular Medicine, George Washington University School of Medicine and Health Sciences, GW Cancer Center, Washington, DC, USA. scholarzy@163.com.
• Zongzhu Li, Department of Biochemistry and Molecular Medicine, George Washington University School of Medicine and Health Sciences, GW Cancer Center, Washington, DC, USA.
• Zhuqing Li, Department of Biochemistry and Molecular Medicine, George Washington University School of Medicine and Health Sciences, GW Cancer Center, Washington, DC, USA.
• Patricia S. Latham, Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Yunxiao Meng, Laboratory & Molecular and Genomic Pathology, Department of Laboratory and Transfusion Services, The George Washington University Hospital, Washington, DC, USA.
• Wen Chen, Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Penghua Yang, Department of Biochemistry and Molecular Medicine, George Washington University School of Medicine and Health Sciences, GW Cancer Center, Washington, DC, USA.
• Chunyan Hou, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
• Junfeng Ma, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
• Wenge Zhu, Department of Biochemistry and Molecular Medicine, George Washington University School of Medicine and Health Sciences, GW Cancer Center, Washington, DC, USA. wz6812@gwu.edu.

Document Type

Journal Article

Publication Date

10-21-2025

Journal

Nature communications

Volume

16

Issue

1

DOI

10.1038/s41467-025-64380-4

Abstract

The nucleotide excision repair (NER) pathway is the primary mechanism for removing UVB-induced photoproducts in mammals. While early steps of NER are well defined, the later step of gap-filling DNA synthesis remains incompletely understood. Here, we report And-1, a DNA replication and repair factor, as a critical regulator of this process. And-1 localizes to UV lesions, directly interacts with the catalytic subunit of DNA polymerase δ (p125), and promotes its recruitment to facilitate repair synthesis. In vitro, And-1 enhances p125 polymerase activity. Importantly, And-1 function in NER requires phosphorylation at T826, which strengthens its binding to both damaged DNA and p125. To evaluate its physiological relevance, we generated phosphorylation-deficient And-1 knock-in mice. These mice exhibited impaired NER and developed keratoacanthomas upon chronic UVB exposure. Collectively, our findings uncover And-1 as a pivotal factor in NER-mediated DNA repair and highlight its role in skin tumorigenesis.

APA Citation

Zhou, Shuyan; Zhang, Yi; Li, Zongzhu; Li, Zhuqing; Latham, Patricia S.; Meng, Yunxiao; Chen, Wen; Yang, Penghua; Hou, Chunyan; Ma, Junfeng; and Zhu, Wenge, "And-1 coordinates with polymerase δ to regulate nucleotide excision repair and UVB-induced skin tumorigenesis" (2025). GW Authored Works. Paper 8249.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8249

Department

Pathology