Rouse John, Jackson Stephen P
The Wellcome Trust/Cancer Research UK Institute (of Cancer and Developmental Biology), University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
Science. 2002 Jul 26;297(5581):547-51. doi: 10.1126/science.1074740.
Left unrepaired, the myriad types of damage that can occur in genomic DNA pose a serious threat to the faithful transmission of the correct complement of genetic material. Defects in DNA damage signaling and repair result in genomic instability, a hallmark of cancer, and often cause lethality, underlining the importance of these processes in the cell and whole organism. The past decade has seen huge advances in our understanding of how the signal transduction pathways triggered by DNA damage radically alter cell behavior. In contrast, it is still unclear how primary DNA damage is detected and how this interfaces with signal transduction and DNA repair proteins.
若不进行修复,基因组DNA可能出现的各种损伤会对正确的遗传物质互补序列的忠实传递构成严重威胁。DNA损伤信号传导和修复方面的缺陷会导致基因组不稳定,这是癌症的一个标志,并且常常会导致细胞死亡,突显了这些过程在细胞和整个生物体中的重要性。在过去十年中,我们对DNA损伤触发的信号转导途径如何从根本上改变细胞行为的理解有了巨大进展。相比之下,目前仍不清楚最初的DNA损伤是如何被检测到的,以及它如何与信号转导和DNA修复蛋白相互作用。