SPIN1 通过促进 Tip60 与 H3K9me3 的结合，促进化疗抗性和 HR 修复。

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-09-01 Epub Date: 2024-08-01 DOI:10.1038/s44319-024-00219-1

Yukun Wang, Mengyao Li, Yuhan Chen, Yuhan Jiang, Ziyu Zhang, Zhenzhen Yan, Xiuhua Liu, Chen Wu

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引用次数: 0

摘要

含串联都铎样结构域的蛋白Spindlin1（SPIN1）是一种转录辅激活因子，在胚胎发育中具有关键功能，并在癌症中发挥着新的作用。然而，SPIN1参与DNA损伤修复的情况仍不清楚。我们的研究表明，SPIN1通过其N端无序区与聚ADP核糖（Poly-ADP-ribose，PAR）结合，被招募到DNA损伤处，促进同源重组（HR）介导的DNA损伤修复。SPIN1 可促进 H3K9me3 在 DNA 损伤位点的积累，并增强 H3K9me3 与 Tip60 之间的相互作用，从而促进 ATM 的激活和 HR 修复。我们还发现，SPIN1 增加了化疗抗性。这些发现揭示了 SPIN1 在激活 H3K9me3 依赖性 DNA 修复途径中的新作用，并表明 SPIN1 可能通过调节双链断裂（DSB）修复的效率来促进癌症的化疗耐受性。

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SPIN1 facilitates chemoresistance and HR repair by promoting Tip60 binding to H3K9me3.

The tandem Tudor-like domain-containing protein Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. However, the involvement of SPIN1 in DNA damage repair has remained unclear. Our study shows that SPIN1 is recruited to DNA lesions through its N-terminal disordered region that binds to Poly-ADP-ribose (PAR), and facilitates homologous recombination (HR)-mediated DNA damage repair. SPIN1 promotes H3K9me3 accumulation at DNA damage sites and enhances the interaction between H3K9me3 and Tip60, thereby promoting the activation of ATM and HR repair. We also show that SPIN1 increases chemoresistance. These findings reveal a novel role for SPIN1 in the activation of H3K9me3-dependent DNA repair pathways, and suggest that SPIN1 may contribute to cancer chemoresistance by modulating the efficiency of double-strand break (DSB) repair.

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.