Department of Biology, Masaryk University, Kamenice 5/A7, Brno 625 00, Czech Republic.
Department of Biology, Masaryk University, Kamenice 5/A7, Brno 625 00, Czech Republic; National Centre for Biomolecular Research, Masaryk University, Kamenice 5/A7, Brno 625 00, Czech Republic; International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, Brno, Czech Republic.
FEBS Lett. 2014 Aug 1;588(15):2446-56. doi: 10.1016/j.febslet.2014.06.010. Epub 2014 Jun 10.
Genomic DNA is constantly challenged from endogenous as well as exogenous sources. The DNA damage response (DDR) mechanism has evolved to combat these challenges and ensure genomic integrity. In this review, we will focus on repair of DNA double-strand breaks (DSB) by homologous recombination and the role of several nucleases and other recombination factors as suitable targets for cancer therapy. Their inactivation as well as overexpression have been shown to sensitize cancer cells by increasing toxicity to DNA-damaging agents and radiation or to be responsible for resistance of cancer cells. These factors can also be used in targeted cancer therapy by taking advantage of specific genetic abnormalities of cancer cells that are not present in normal cells and that result in cancer cell lethality.
基因组 DNA 不断受到内源性和外源性因素的挑战。DNA 损伤反应 (DDR) 机制的进化是为了应对这些挑战，确保基因组的完整性。在这篇综述中，我们将重点讨论同源重组修复 DNA 双链断裂 (DSB) 的机制，以及几种核酸酶和其他重组因子作为癌症治疗的合适靶点的作用。它们的失活和过表达已被证明通过增加对 DNA 损伤剂和辐射的毒性来使癌细胞敏感，或者导致癌细胞耐药。这些因素也可以通过利用癌细胞中特有的、正常细胞中不存在的特定遗传异常来进行靶向癌症治疗，从而导致癌细胞死亡。
