DNA损伤
DNA修复
纤维蛋白
生物
细胞生物学
癌变
DNA
同源重组
分子生物学
癌症研究
癌症
化学
核糖核酸
遗传学
基因
作者
Xiaorui Sun,Congwen Gao,Xin Xu,Mengyuan Li,Xinhua Zhao,Y Wang,Yuhang Li,Shun Zhang,Zhong Yan,Xiuhua Liu,Chen Wu
标识
DOI:10.15252/embr.202256230
摘要
Fibrillarin (FBL) is a highly conserved nucleolar methyltransferase responsible for methylation of ribosomal RNA and proteins. Here, we reveal a role for FBL in DNA damage response and its impact on cancer proliferation and sensitivity to DNA-damaging agents. FBL is highly expressed in various cancers and correlates with poor survival outcomes in cancer patients. Knockdown of FBL sensitizes tumor cells and xenografts to DNA crosslinking agents, and leads to homologous recombination-mediated DNA repair defects. We identify Y-box-binding protein-1 (YBX1) as a key interacting partner of FBL, and FBL increases the nuclear accumulation of YBX1 in response to DNA damage. We show that FBL promotes the expression of BRCA1 by increasing the binding of YBX1 to the BRCA1 promoter. Our study sheds light on the regulatory mechanism of FBL in tumorigenesis and DNA damage response, providing potential therapeutic targets to overcome chemoresistance in cancer.
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