ArticlebioRxiv : the preprint server for biology2026
Orchestrated metal ion repositioning defines the dynamic catalytic strategy of the essential DNA repair nuclease APE1.
Leonardo F Serafim, Susan E Tsutakawa, Andrew S Arvai, Bradley R Kossmann, Anil K Mantha, Rachel Abbotts, David M Wilson, Sankar Mitra, John A Tainer, Ivaylo Ivanov
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
10 authors.
Leonardo F SerafimDepartment of Chemistry, Georgia State University, Atlanta, Georgia, USA.
Susan E TsutakawaMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Andrew S ArvaiIntegrative Structural & Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Bradley R KossmannDepartment of Chemistry, Georgia State University, Atlanta, Georgia, USA.
Anil K ManthaThe University of Texas Medical Branch, Galveston, TX, USA.
Rachel AbbottsDepartment of Medical Oncology, WVU School of Medicine, West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA.
David M WilsonBiomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
Sankar MitraDivision of DNA Repair Research, Center for Neuroregeneration, Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX 77030, United States.
John A TainerMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California, USA.ORCID 0000-0003-1659-2429 Funding
Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6MMesoscale and Nanoscale Technologies Integrated by Structures for DNA Repair Complexes (MANTIS-DRC)R35CA220430 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI John A. Tainer · 2018 to 2026
$7.6MSTRUCTURE AND FUNCTION OF METALLOENZYMES FOR DNA REPAIRR01GM046312 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI TAINER, JOHN A. · 1991 to 2012
$5.9MAdvanced Computational Modeling of Molecular Machines in Gene Regulation and DNA RepairR35GM139382 · NIGMS · GEORGIA STATE UNIVERSITY · PI IVANOV, IVAYLO NIKOLAEV · 2021 to 2025
$2.0MIntegrative Modeling of Biomolecular Machinery in Nucleotide Excision RepairR01ES032786 · NIEHS · GEORGIA STATE UNIVERSITY · PI Ivaylo Nikolaev Ivanov · 2022 to 2026
$1.7MNCI NIH HHS P01 CA092584NCI NIH HHS R35 CA220430NIEHS NIH HHS R01 ES032786NIGMS NIH HHS R01 GM046312NIGMS NIH HHS R35 GM139382
6 · The paper itselfAbstract
Human AP-endonuclease 1 (APE1) is a vital enzyme in the base excision repair pathway that protects genome stability by eliminating ubiquitous abasic DNA lesions. Despite its importance and therapeutic potential, how APE1 achieves high specificity and single-metal-ion catalytic efficiency remains unclear. Here, we present a high-resolution structure of the APE1-DNA Michaelis complex coordinated with physiological cofactor Mg
Indexed as
ab initio molecular dynamicsbase excision repaircancer etiologygenome maintenancemetalloenzymesnuclease reaction mechanismphosphoryl transferQM/MM
Identifiers
PMID42182258
PMCPMC13192912
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