含有串联 Tudor 结构域的蛋白 Spindlin1 (SPIN1) 是一种转录共激活因子，在胚胎发育和癌症中发挥重要作用。然而，SPIN1 在 DNA 损伤修复中的作用仍不清楚。我们的研究表明，SPIN1 通过其 N 端无序区域与聚 ADP 核糖 (PAR) 结合而被招募到 DNA 损伤处，并促进同源重组 (HR) 介导的 DNA 损伤修复。 SPIN1促进H3K9me3在DNA损伤位点积累，并增强H3K9me3与Tip60之间的相互作用，从而促进ATM和HR修复的激活。我们还表明 SPIN1 会增加化疗耐药性。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化疗耐药性。© 2024。 。

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.© 2024. The Author(s).