The mechanistic role of polyamines in DNA double-strand break repair

• Main Authors: Chih-Ying Lee, 李致瑩
• Other Authors: 冀宏源
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/kr6ppe

博士 === 國立臺灣大學 === 生化科學研究所 === 106 === How naturally occurring cellular small chemicals impact upon genome integrity is of great interests in cancer biology. Many cancers synthesize elevated levels of polyamines to sustain cell growth and proliferation, thus implicating these compounds in tumorigenesis. Here, we document a novel function of polyamines in DNA double-strand break (DSB) repair. Specifically, we show that polyamines facilitate homologous recombination-mediated DSB repair without affecting non-homologous DNA end-joining. Biochemical reconstitution and functional analyses demonstrate that polyamines significantly enhance the DNA strand exchange activity of RAD51. The stimulatory effect of polyamines by RAD51 stems from the enhancement of duplex DNA capture in the DNA homology search process. We also reveal the importance of polyamines to DSB repair in an animal model. Our findings thus furnish valuable insights into the role of polyamines in genome maintenance via homology-directed DNA repair.