2. Academic Validation
  3. UHRF1-mediated ubiquitination of nonhomologous end joining factor XLF promotes DNA repair in human tumor cells

UHRF1-mediated ubiquitination of nonhomologous end joining factor XLF promotes DNA repair in human tumor cells

  • J Biol Chem. 2024 Sep 27;300(11):107823. doi: 10.1016/j.jbc.2024.107823.
Zhiwen Deng 1,  Caiyun Long 1,  Shuzhen Han 1,  Zhishen Xu 2,  Teng Hou 3,  Weili Li 1,  Xingwu Wang 4,  Xiangyu Liu 5
Affiliations

Affiliations

  • 1 International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen, China.
  • 2 International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen, China; South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China.
  • 3 South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China.
  • 4 Molecular Cancer Research Center, School of Medicine, Sun Yat-Sen University, Shenzhen, Guangdong, China. Electronic address: wxwbio@mail.ustc.edu.cn.
  • 5 International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen, China; Department of Hematology, The Second People's Hospital of Shenzhen, Shenzhen, China. Electronic address: liuxiangyu@szu.edu.cn.
PMID: 39341501 DOI: 10.1016/j.jbc.2024.107823
Abstract

UHRF1 (Ubiquitin-like with PHD and Ring Finger domains 1) is a crucial E3 ubiquitin Ligase and epigenetic regulator with pivotal roles in various biological processes, including the maintenance of DNA methylation, regulation of gene expression, and facilitation of DNA damage repair. In this study, we unveil that UHRF1 interacts with the nonhomologous end joining factor XLF (also known as Cernunnos) following DNA double strand breaks in HeLa cells. Furthermore, we demonstrate that UHRF1 catalyzes lysine 63-linked polyubiquitination of XLF, rather than lysine 48-linked polyubiquitination. Notably, this polyubiquitination of XLF by UHRF1 does not affect its protein stability; instead, it enhances the recruitment of XLF to the sites of DNA damage. These findings shed light on the role of UHRF1 as a novel regulator of DNA repair through XLF in tumor cells.

Keywords

DNA repair; K63; UHRF1; XLF; ubiquitination.

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