FBL promotes cancer cell resistance to DNA damage and BRCA1 transcription via YBX1.

Xiaorui Sun, Congwen Gao, Xin Xu, Mengyuan Li, Xinhua Zhao, Yanan Wang, Yun Wang, Shun Zhang, Zhenzhen Yan, Xiuhua Liu, Chen Wu

EMBO reports 2023 Sep 06

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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. © 2023 The Authors.

Citation

Xiaorui Sun, Congwen Gao, Xin Xu, Mengyuan Li, Xinhua Zhao, Yanan Wang, Yun Wang, Shun Zhang, Zhenzhen Yan, Xiuhua Liu, Chen Wu. FBL promotes cancer cell resistance to DNA damage and BRCA1 transcription via YBX1. EMBO reports. 2023 Sep 06;24(9):e56230