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

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

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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)path-way.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 selec-tively 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 res-olution 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.

ILF3RNA:DNA hybridstelomeric R-loopshomologous recombinationtelomeric DNA damage responses

Chuanle Wang、Yan Huang、Yue Yang、Ruofei Li、Yingying Li、Hongxin Qiu、Jiali Wu、Guang Shi、Wenbin Ma、Zhou Songyang

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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

Department of Nephrology,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China

National Natural Science FoundationNational Natural Science FoundationNational Natural Science FoundationNational Natural Science FoundationNational Natural Science FoundationNational Natural Science FoundationNational Key Research and Development Program of ChinaGuang Dong Basic and Applied Basic Research Foundation

8227159881871109820715873193005832330023321707572018YFA01070032020A1515010462

2024

10.1093/procel/pwad054

蛋白质与细胞

蛋白质与细胞

CSTPCD
影响因子：0.645
ISSN：
年,卷(期)：2024.15(7)