ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader

doi:10.1093/procel/pwad054

Protein & Cell

2024, Vol. 15

Issue (7): 493-511 https://doi.org/10.1093/procel/pwad054

本期目录

ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader

Chuanle Wang^1,², Yan Huang¹(

), Yue Yang^1,³, Ruofei Li¹, Yingying Li¹, Hongxin Qiu¹, Jiali Wu¹, Guang Shi¹, Wenbin Ma¹, Zhou Songyang^1,²(

)

¹. 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
². Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510275, China
³. Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

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Abstract：

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.

Key words： ILF3 RNA:DNA hybrids telomeric R-loops homologous recombination telomeric DNA damage responses

收稿日期: 2023-04-19 出版日期: 2024-07-31

Corresponding Author(s): Yan Huang,Zhou Songyang

引用本文:

. [J]. Protein & Cell, 2024, 15(7): 493-511.
Chuanle Wang, Yan Huang, Yue Yang, Ruofei Li, Yingying Li, Hongxin Qiu, Jiali Wu, Guang Shi, Wenbin Ma, Zhou Songyang. ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader. Protein Cell, 2024, 15(7): 493-511.

链接本文:

https://academic.hep.com.cn/pac/CN/10.1093/procel/pwad054
https://academic.hep.com.cn/pac/CN/Y2024/V15/I7/493

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