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

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

机构地区：[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

出　　处：《Protein & Cell》2024年第7期493-511,共19页蛋白质与细胞（英文版）

基　　金：National Natural Science Foundation(Grant Nos.82271598,81871109,82071587,31930058,32330023 and 32170757);National Key Research and Development Program of China(2018YFA0107003);Guang Dong Basic and Applied Basic Research Foundation(2020A1515010462).

摘　　要：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.

关 键 词：ILF3 RNA:DNA hybrids telomeric R-loops homologous recombination telomeric DNA damage responses 

分 类 号：Q23[生物学—细胞生物学]