FBL Promotes Cancer Cell Resistance to DNA Damage and BRCA1 Transcription Via YBX1

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2023 Jul 25

PMID 37489617

Authors

Xiaorui Sun

Congwen Gao

Xin Xu

Mengyuan Li

Xinhua Zhao

Yanan Wang

Yun Wang

Shun Zhang

Zhenzhen Yan

Xiuhua Liu

Chen Wu

Affiliations

Soon will be listed here.

Abstract

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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