دورية أكاديمية
ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader.
العنوان: | ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader. |
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المؤلفون: | Wang C; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China.; Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510275, China., Huang Y; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China., Yang Y; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China.; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China., Li R; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China., Li Y; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China., Qiu H; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China., Wu J; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China., Shi G; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China., Ma W; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China., Songyang Z; MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol and Guangzhou Key Laboratory of Healthy Aging, School of Lifesciences, Sun Yat-sen University, Guangzhou 510275, China.; Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510275, China. |
المصدر: | Protein & cell [Protein Cell] 2024 Jul 01; Vol. 15 (7), pp. 493-511. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Oxford University Press Country of Publication: Germany NLM ID: 101532368 Publication Model: Print Cited Medium: Internet ISSN: 1674-8018 (Electronic) Linking ISSN: 1674800X NLM ISO Abbreviation: Protein Cell Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2023- : [Oxford] : Oxford University Press Original Publication: Heidelberg : Beijing, China : Springer ; Higher Education Press |
مواضيع طبية MeSH: | Telomere*/metabolism , Telomere*/genetics , Nuclear Factor 90 Proteins*/metabolism , Nuclear Factor 90 Proteins*/genetics , Homologous Recombination* , R-Loop Structures*/genetics, Humans ; DEAD-box RNA Helicases/metabolism ; DEAD-box RNA Helicases/genetics ; HEK293 Cells ; Telomere Homeostasis |
مستخلص: | Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability. The telomeric repeat-containing RNA (TERRA) that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop. In tumor cells, R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres (ALT) pathway. Dysregulated R-loops can cause stalled replication forks and telomere instability. However, how R-loops are recognized and regulated, particularly at telomeres, is not well understood. We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination. Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses. In addition, ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway. Using the proximity-dependent biotin identification (BioID) technology, we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases, including DHX9. Importantly, ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9. Our findings suggest that ILF3 may function as a reader of telomeric R-loops, helping to prevent abnormal homologous recombination and maintain telomere homeostasis. (© The Author(s) 2023. Published by Oxford University Press on behalf of Higher Education Press.) |
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معلومات مُعتمدة: | 82271598, 81871109, 82071587, 31930058, 32330023 and 32170757 National Natural Science Foundation; 2018YFA0107003 National Key Research and Development Program of China; 2020A1515010462 Guang Dong Basic and Applied Basic Research Foundation |
فهرسة مساهمة: | Keywords: ILF3; RNA:DNA hybrids; homologous recombination; telomeric DNA damage responses; telomeric R-loops |
المشرفين على المادة: | 0 (Nuclear Factor 90 Proteins) 0 (ILF3 protein, human) EC 3.6.4.13 (DEAD-box RNA Helicases) |
تواريخ الأحداث: | Date Created: 20231122 Date Completed: 20240630 Latest Revision: 20240722 |
رمز التحديث: | 20240722 |
مُعرف محوري في PubMed: | PMC11214836 |
DOI: | 10.1093/procel/pwad054 |
PMID: | 37991243 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1674-8018 |
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DOI: | 10.1093/procel/pwad054 |