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

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

引用次数: 0

Abstract

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

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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

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