دورية أكاديمية
أعرض في EDS

Distinct regulation of ATM signaling by DNA single-strand breaks and APE1.

التفاصيل البيبلوغرافية
العنوان: Distinct regulation of ATM signaling by DNA single-strand breaks and APE1.
المؤلفون: Zhao H; Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA., Li J; Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA., You Z; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, 63110, USA., Lindsay HD; Lancaster Medical School, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ, UK., Yan S; Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA. shan.yan@charlotte.edu.; School of Data Science, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA. shan.yan@charlotte.edu.; Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, USA. shan.yan@charlotte.edu.
المصدر: Nature communications [Nat Commun] 2024 Aug 07; Vol. 15 (1), pp. 6517. Date of Electronic Publication: 2024 Aug 07.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Ataxia Telangiectasia Mutated Proteins*/metabolism , Ataxia Telangiectasia Mutated Proteins*/genetics , DNA Breaks, Single-Stranded* , Signal Transduction* , DNA-(Apurinic or Apyrimidinic Site) Lyase*/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase*/genetics, Animals ; Xenopus Proteins/metabolism ; Xenopus Proteins/genetics ; Humans ; Xenopus laevis ; DNA Repair
مستخلص: In response to DNA double-strand breaks or oxidative stress, ATM-dependent DNA damage response (DDR) is activated to maintain genome integrity. However, it remains elusive whether and how DNA single-strand breaks (SSBs) activate ATM. Here, we provide direct evidence in Xenopus egg extracts that ATM-mediated DDR is activated by a defined SSB structure. Our mechanistic studies reveal that APE1 promotes the SSB-induced ATM DDR through APE1 exonuclease activity and ATM recruitment to SSB sites. APE1 protein can form oligomers to activate the ATM DDR in Xenopus egg extracts in the absence of DNA and can directly stimulate ATM kinase activity in vitro. Our findings reveal distinct mechanisms of the ATM-dependent DDR activation by SSBs in eukaryotic systems and identify APE1 as a direct activator of ATM kinase.
(© 2024. The Author(s).)
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معلومات مُعتمدة: R03 CA270663 United States CA NCI NIH HHS; Seed Grants UNC | University of North Carolina at Charlotte (UNC Charlotte); R03CA270663 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); R21ES032966 U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS); R21 ES032966 United States ES NIEHS NIH HHS; R01 CA225637 United States CA NCI NIH HHS; CR782 North West Cancer Research Fund (NWCR); R01CA225637 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
المشرفين على المادة: EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase)
0 (Xenopus Proteins)
تواريخ الأحداث: Date Created: 20240807 Date Completed: 20240807 Latest Revision: 20240810
رمز التحديث: 20240812
مُعرف محوري في PubMed: PMC11306256
DOI: 10.1038/s41467-024-50836-6
PMID: 39112456
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-50836-6