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
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
