Mills Kevin D, Ferguson David O, Alt Frederick W
The Center for Blood Research, Boston, MA, USA.
Immunol Rev. 2003 Aug;194:77-95. doi: 10.1034/j.1600-065x.2003.00060.x.
DNA double-strand breaks (DSBs) represent dangerous chromosomal lesions that can lead to mutation, neoplastic transformation, or cell death. DSBs can occur by extrinsic insult from environmental sources or may occur intrinsically as a result of cellular metabolism or a genetic program. Mammalian cells possess potent and efficient mechanisms to repair DSBs, and thus complete normal development as well as mitigate oncogenic potential and prevent cell death. When DSB repair (DSBR) fails, chromosomal instability results and can be associated with tumor formation or progression. Studies of mice deficient in various components of the non-homologous end joining pathway of DSBR have revealed key roles in both the developmental program of B and T lymphocytes as well as in the maintenance of general genome stability. Here, we review the current thinking about DSBs and DSBR in chromosomal instability and tumorigenesis, and we highlight the implications for understanding the karyotypic features associated with human tumors.
DNA双链断裂（DSB）是危险的染色体损伤，可导致突变、肿瘤转化或细胞死亡。DSB可因环境来源的外在损伤而发生，也可能由于细胞代谢或遗传程序而内在发生。哺乳动物细胞拥有强大而有效的机制来修复DSB，从而完成正常发育，并减轻致癌潜力，防止细胞死亡。当DSB修复（DSBR）失败时，会导致染色体不稳定，并可能与肿瘤形成或进展相关。对DSBR非同源末端连接途径中各种成分缺陷的小鼠的研究揭示了其在B和T淋巴细胞发育程序以及维持一般基因组稳定性方面的关键作用。在这里，我们综述了目前关于染色体不稳定和肿瘤发生中DSB和DSBR的看法，并强调了对理解与人类肿瘤相关的核型特征的意义。
