Institute of Biochemical Sciences, National Taiwan University, Taipei, 10617, Taiwan.
Department of Biomedical Engineering, National Taiwan University, Taipei, 10617, Taiwan.
Nat Commun. 2019 Jan 8;10(1):65. doi: 10.1038/s41467-018-08011-1.
Polyamines, often elevated in cancer cells, have been shown to promote cell growth and proliferation. Whether polyamines regulate other cell functions remains unclear. Here, we explore whether and how polyamines affect genome integrity. When DNA double-strand break (DSB) is induced in hair follicles by ionizing radiation, reduction of cellular polyamines augments dystrophic changes with delayed regeneration. Mechanistically, polyamines facilitate homologous recombination-mediated DSB repair without affecting repair via non-homologous DNA end-joining and single-strand DNA annealing. Biochemical reconstitution and functional analyses demonstrate that polyamines enhance the DNA strand exchange activity of RAD51 recombinase. The effect of polyamines on RAD51 stems from their ability to enhance the capture of homologous duplex DNA and synaptic complex formation by the RAD51-ssDNA nucleoprotein filament. Our work demonstrates a novel function of polyamines in the maintenance of genome integrity via homology-directed DNA repair.
多胺通常在癌细胞中升高，已被证明能促进细胞生长和增殖。多胺是否调节其他细胞功能尚不清楚。在这里，我们探讨多胺是否以及如何影响基因组完整性。当毛囊中的 DNA 双链断裂 (DSB) 被电离辐射诱导时，细胞多胺的减少会加剧退行性变化，导致再生延迟。从机制上讲，多胺促进同源重组介导的 DSB 修复，而不影响非同源 DNA 末端连接和单链 DNA 退火介导的修复。生化重建和功能分析表明，多胺增强 RAD51 重组酶的 DNA 链交换活性。多胺对 RAD51 的影响源于其增强 RAD51-ssDNA 核蛋白丝捕获同源双链 DNA 和突触复合物形成的能力。我们的工作证明了多胺通过同源定向 DNA 修复在维持基因组完整性方面的新功能。
