Frosina Guido
Molecular Mutagenesis & DNA Repair Unit, Istituto Nazionale Ricerca Cancro, 16132 Genova, Italy.
J Biomed Biotechnol. 2010;2010:845396. doi: 10.1155/2010/845396. Epub 2010 Apr 8.
DNA repair is a double-edged sword in stem cells. It protects normal stem cells in both embryonic and adult tissues from genetic damage, thus allowing perpetuation of intact genomes into new tissues. Fast and efficient DNA repair mechanisms have evolved in normal stem and progenitor cells. Upon differentiation, a certain degree of somatic mutations becomes more acceptable and, consequently, DNA repair dims. DNA repair turns into a problem when stem cells transform and become cancerous. Transformed stem cells drive growth of a number of tumours (e.g., high grade gliomas) and being particularly resistant to chemo- and radiotherapeutic agents often cause relapses. The contribution of DNA repair to resistance of these tumour-driving cells is the subject of intense research, in order to find novel agents that may sensitize them to chemotherapy and radiotherapy.
DNA修复在干细胞中是一把双刃剑。它保护胚胎和成体组织中的正常干细胞免受基因损伤,从而使完整的基因组能够延续到新的组织中。正常的干细胞和祖细胞已经进化出快速高效的DNA修复机制。在分化过程中,一定程度的体细胞突变变得更易被接受,因此DNA修复能力减弱。当干细胞发生转化并癌变时,DNA修复就会成为一个问题。转化后的干细胞会促使多种肿瘤(如高级别胶质瘤)生长,并且它们对化疗和放疗药物具有特别的抗性,常常导致复发。DNA修复对这些驱动肿瘤生长的细胞的抗性所起的作用是深入研究的课题,目的是找到能使它们对化疗和放疗敏感的新型药物。