دورية أكاديمية
Impact of DNA ligase 1 and IIIα interactions with APE1 and polβ on the efficiency of base excision repair pathway at the downstream steps.
| العنوان: | Impact of DNA ligase 1 and IIIα interactions with APE1 and polβ on the efficiency of base excision repair pathway at the downstream steps. |
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| المؤلفون: | Almohdar D; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA., Murcia D; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA., Tang Q; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA., Ortiz A; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA., Martinez E; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA., Parwal T; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA., Kamble P; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA., Çağlayan M; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA. Electronic address: caglayanm@ufl.edu. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2024 Jun; Vol. 300 (6), pp. 107355. Date of Electronic Publication: 2024 May 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | DNA Ligase ATP*/metabolism , DNA Ligase ATP*/genetics , DNA Ligase ATP*/chemistry , DNA Polymerase beta*/metabolism , DNA Polymerase beta*/chemistry , DNA Repair* , DNA-(Apurinic or Apyrimidinic Site) Lyase*/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase*/chemistry , DNA-(Apurinic or Apyrimidinic Site) Lyase*/genetics, Excision Repair ; Poly-ADP-Ribose Binding Proteins ; Protein Binding |
| مستخلص: | Base excision repair (BER) requires a tight coordination between the repair enzymes through protein-protein interactions and involves gap filling by DNA polymerase (pol) β and subsequent nick sealing by DNA ligase (LIG) 1 or LIGIIIα at the downstream steps. Apurinic/apyrimidinic-endonuclease 1 (APE1), by its exonuclease activity, proofreads 3' mismatches incorporated by polβ during BER. We previously reported that the interruptions in the functional interplay between polβ and the BER ligases result in faulty repair events. Yet, how the protein interactions of LIG1 and LIGIIIα could affect the repair pathway coordination during nick sealing at the final steps remains unknown. Here, we demonstrate that LIGIIIα interacts more tightly with polβ and APE1 than LIG1, and the N-terminal noncatalytic region of LIG1 as well as the catalytic core and BRCT domain of LIGIIIα mediate interactions with both proteins. Our results demonstrated less efficient nick sealing of polβ nucleotide insertion products in the absence of LIGIIIα zinc-finger domain and LIG1 N-terminal region. Furthermore, we showed a coordination between APE1 and LIG1/LIGIIIα during the removal of 3' mismatches from the nick repair intermediate on which both BER ligases can seal noncanonical ends or gap repair intermediate leading to products of single deletion mutagenesis. Overall results demonstrate the importance of functional coordination from gap filling by polβ coupled to nick sealing by LIG1/LIGIIIα in the presence of proofreading by APE1, which is mainly governed by protein-protein interactions and protein-DNA intermediate communications, to maintain repair efficiency at the downstream steps of the BER pathway. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: AP-endonuclease 1; DNA ligase 1; DNA ligase IIIα; DNA polymerase β; DNA repair; base excision repair; genome stability; protein-DNA binding; protein–protein interaction |
| المشرفين على المادة: | EC 6.5.1.1 (DNA Ligase ATP) EC 2.7.7.7 (DNA Polymerase beta) EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase) 0 (Poly-ADP-Ribose Binding Proteins) |
| تواريخ الأحداث: | Date Created: 20240508 Date Completed: 20240702 Latest Revision: 20240717 |
| رمز التحديث: | 20240718 |
| مُعرف محوري في PubMed: | PMC11176775 |
| DOI: | 10.1016/j.jbc.2024.107355 |
| PMID: | 38718860 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2024.107355 |