The interaction between ALKBH2 DNA repair enzyme and PCNA is direct, mediated by the hydrophobic pocket of PCNA and perturbed in naturally-occurring ALKBH2 variants
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Author(s)
Hübscher, Ullrich
Fu, Dragony
Samson, Leona D
Van Loon, Barbara
Date Issued
September 2015
Journal
DNA Repair
Publisher
Elsevier
Citation
Fu, Dragony, Leona D. Samson, Ullrich Hübscher, and Barbara van Loon. “The Interaction Between ALKBH2 DNA Repair Enzyme and PCNA Is Direct, Mediated by the Hydrophobic Pocket of PCNA and Perturbed in Naturally-Occurring ALKBH2 Variants.” DNA Repair 35 (November 2015): 13–18.
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Author's final manuscript
Abstract
Human AlkB homolog 2 (ALKBH2) is a DNA repair enzyme that catalyzes the direct reversal of DNA methylation damage through oxidative demethylation. While ALKBH2 colocalizes with proliferating cell nuclear antigen (PCNA) in DNA replication foci, it remains unknown whether these two proteins alone form a complex or require additional components for interaction. Here, we demonstrate that ALKBH2 can directly interact with PCNA independent from other cellular factors, and we identify the hydrophobic pocket of PCNA as the key domain mediating this interaction. Moreover, we find that PCNA association with ALKBH2 increases significantly during DNA replication, suggesting that ALKBH2 forms a cell-cycle dependent complex with PCNA. Intriguingly, we show that an ALKBH2 germline variant, as well as a variant found in cancer, display altered interaction with PCNA. Our studies reveal the ALKBH2 binding interface of PCNA and indicate that both germline and somatic ALKBH2 variants could have cellular effects on ALKBH2 function in DNA repair.
MIT Department
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.dnarep.2015.09.008
