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Updated: Jan 14, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
And-1 coordinates with polymerase δ to regulate nucleotide excision repair and UVB-induced skin tumorigenesis
Shuyan Zhou1, Yi Zhang2, Zongzhu Li1
1Department of Biochemistry and Molecular Medicine, George Washington University School of Medicine and Health Sciences, GW Cancer Center, Washington, DC, USA.
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.
Insights
And-1 is a crucial DNA repair factor that fills gaps during nucleotide excision repair (NER). Its phosphorylation regulates this process, preventing skin tumors caused by UV damage.
Area of Science:
- Molecular Biology
- DNA Repair Mechanisms
- Cancer Biology
Background:
- The nucleotide excision repair (NER) pathway removes DNA damage from ultraviolet (UV) radiation.
- The gap-filling DNA synthesis step in NER is not fully understood.
Purpose of the Study:
- To identify and characterize novel regulators of DNA synthesis during NER.
- To investigate the role of And-1 in DNA repair and skin cancer prevention.
Main Methods:
- Localization studies of And-1 to UV lesions.
- In vitro biochemical assays to assess And-1 interaction with DNA polymerase δ (p125).
- Generation and analysis of phosphorylation-deficient And-1 knock-in mice.
Main Results:
- And-1 localizes to UV lesions and interacts with p125, promoting repair synthesis.
- And-1 phosphorylation at T826 is critical for its function in NER.
- And-1 deficient mice show impaired NER and increased susceptibility to UVB-induced skin tumors.
Conclusions:
- And-1 is a key regulator of gap-filling DNA synthesis in the NER pathway.
- And-1's role in DNA repair is essential for preventing UVB-induced skin tumorigenesis.
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