The repair of DNA double-strand breaks (DSBs) through homologous recombination (HR) is vital for maintaining the stability and integrity of the genome. RNA binding proteins (RBPs) intricately regulate the DNA damage repair process, yet the precise molecular mechanisms underlying their function remain incompletely understood. In this study, we highlight the pivotal role of RPS15, a representative RBP, in homologous recombination repair. Specifically, we demonstrate that RPS15 promotes DNA end resection, a crucial step in homologous recombination. Notably, we identify an interaction between RPS15 and CtIP, a key factor in homologous recombination repair. This interaction is essential for CtIP recruitment to DSB sites, subsequent RPA coating, and RAD51 replacement, all critical steps in efficient homologous recombination repair and conferring resistance to genotoxic treatments. Functionally, suppressing RPS15 expression sensitizes cancer cells to X-ray radiation and enhances the therapeutic synergistic effect of PARP1 inhibitors in breast cancer cells. In summary, our findings reveal that RPS15 promotes DNA end resection to ensure effective homologous recombination repair, suggesting its potential as a therapeutic target in cancer treatment.
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November 2024
REGULAR ARTICLES|
November 08 2024
RPS15 Coordinates with CtIP to Facilitate Homologous Recombination and Confer Therapeutic Resistance in Breast Cancer
Baohang Lin;
Baohang Lin
aDepartment of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
bDepartment of Thyroid, Breast and Vascular Surgery, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
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Guan Huang;
Guan Huang
cDepartment of Pathology, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
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Zishan Yuan;
Zishan Yuan
bDepartment of Thyroid, Breast and Vascular Surgery, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
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Xun Peng;
Xun Peng
bDepartment of Thyroid, Breast and Vascular Surgery, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
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Chunliang Yu;
Chunliang Yu
bDepartment of Thyroid, Breast and Vascular Surgery, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
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Jialu Zheng;
Jialu Zheng
bDepartment of Thyroid, Breast and Vascular Surgery, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
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Zequn Li;
Zequn Li
bDepartment of Thyroid, Breast and Vascular Surgery, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
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Juanyun Li;
Juanyun Li
bDepartment of Thyroid, Breast and Vascular Surgery, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
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Jinan Liang;
Jinan Liang
bDepartment of Thyroid, Breast and Vascular Surgery, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
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Bo Xu
Bo Xu
1
aDepartment of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
dDepartment of Thyroid and Breast Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China
1Corresponding author: Dr. Bo Xu, Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China; email: [email protected]
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Radiat Res (2024) 202 (5): 775–784.
Article history
Received:
May 13 2024
Accepted:
September 24 2024
Citation
Baohang Lin, Guan Huang, Zishan Yuan, Xun Peng, Chunliang Yu, Jialu Zheng, Zequn Li, Juanyun Li, Jinan Liang, Bo Xu; RPS15 Coordinates with CtIP to Facilitate Homologous Recombination and Confer Therapeutic Resistance in Breast Cancer. Radiat Res 1 November 2024; 202 (5): 775–784. doi: https://doi.org/10.1667/RADE-24-00134.1
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