ArticleProceedings of the National Academy of Sciences of the United States of America2017
APE2 Zf-GRF facilitates 3'-5' resection of DNA damage following oxidative stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 58 citations in OpenAlex.
- Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting.NAR cancer · 2025Review
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- Distinct regulation of ATM signaling by DNA single-strand breaks and APE1.Nature communications · 2024Article
- Serum Extracellular Vesicles Cargo Approach in Bitches with Mammary Tumors.Current issues in molecular biology · 2024Article
- Review
- Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life.Cells · 2024Review
- Zinc finger knuckle genes are associated with tolerance to drought and dehydration in chickpea (Frontiers in plant science · 2024Article
- Inner Amino Acid Contacts Are Key Factors of Multistage Structural Rearrangements of DNA and Affect Substrate Specificity of Apurinic/Apyrimidinic Endonuclease APE1.International journal of molecular sciences · 2023Article
- Novel mechanisms for the removal of strong replication-blocking HMCES- and thiazolidine-DNA adducts in humans.Nucleic acids research · 2023Article
- APE2 Promotes AID-Dependent Somatic Hypermutation in Primary B Cell Cultures That Is Suppressed by APE1.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Article
- The APE2 nuclease is essential for DNA double-strand break repair by microhomology-mediated end joining.Molecular cell · 2023Article
- Model of abasic site DNA cross-link repair; from the architecture of NEIL3 DNA binding domains to the X-structure model.Nucleic acids research · 2022Article
- APE1 assembles biomolecular condensates to promote the ATR-Chk1 DNA damage response in nucleolus.Nucleic acids research · 2022Article
- Molecular basis for processing of topoisomerase 1-triggered DNA damage by Apn2/APE2.Cell reports · 2022Article
- Microbial Type IA Topoisomerase C-Terminal Domain Sequence Motifs, Distribution and Combination.International journal of molecular sciences · 2022Article
- Noncatalytic Domains in DNA Glycosylases.International journal of molecular sciences · 2022Review
- The APE2 Exonuclease Is a Client of the Hsp70-Hsp90 Axis in Yeast and Mammalian Cells.Biomolecules · 2022Article
- Species variations in XRCC1 recruitment strategies for FHA domain-containing proteins.DNA repair · 2022Article
- Genome-wide identification of growth-regulating factor transcription factor family related to leaf and stem development in alfalfa.Frontiers in plant science · 2022Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The Xenopus laevis APE2 (apurinic/apyrimidinic endonuclease 2) nuclease participates in 3'-5' nucleolytic resection of oxidative DNA damage and activation of the ATR-Chk1 DNA damage response (DDR) pathway via ill-defined mechanisms. Here we report that APE2 resection activity is regulated by DNA interactions in its Zf-GRF domain, a region sharing high homology with DDR proteins Topoisomerase 3α (TOP3α) and NEIL3 (Nei-like DNA glycosylase 3), as well as transcription and RNA regulatory proteins, such as TTF2 (transcription termination factor 2), TFIIS, and RPB9. Biochemical and NMR results establish the nucleic acid-binding activity of the Zf-GRF domain. Moreover, an APE2 Zf-GRF X-ray structure and small-angle X-ray scattering analyses show that the Zf-GRF fold is typified by a crescent-shaped ssDNA binding claw that is flexibly appended to an APE2 endonuclease/exonuclease/phosphatase (EEP) catalytic core. Structure-guided Zf-GRF mutations impact APE2 DNA binding and 3'-5' exonuclease processing, and also prevent efficient APE2-dependent RPA recruitment to damaged chromatin and activation of the ATR-Chk1 DDR pathway in response to oxidative stress in Xenopus egg extracts. Collectively, our data unveil the APE2 Zf-GRF domain as a nucleic acid interaction module in the regulation of a key single-strand break resection function of APE2, and also reveal topologic similarity of the Zf-GRF to the zinc ribbon domains of TFIIS and RPB9.
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