Gilchrest Barbara A, Eller Mark S
Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
J Investig Dermatol Symp Proc. 2005 Nov;10(2):124-30. doi: 10.1111/j.1087-0024.2005.200406.x.
Work in many laboratories over the past decade has established a central role for the telomere in maintaining genomic integrity. Available data may be interpreted to indicate that telomere disruption, whether due to acute DNA damage or progressive telomere shortening, is the initial event that triggers multiple DNA damage responses. The specific initiating event is likely exposure of the otherwise concealed single-stranded 3' overhang, tandem repeats of TTAGGG, a signal that can be provided to cells in the absence of DNA damage by exogenously provided T-oligos. The ability of T-oligo treatment to trigger SOS-like responses and/or to cause selective apoptosis of already malignantly transformed cells may provide an important new means of cancer prevention and treatment.
在过去十年里,许多实验室的研究都证实了端粒在维持基因组完整性方面的核心作用。现有数据可以解释为,端粒破坏,无论是由于急性DNA损伤还是渐进性端粒缩短,都是触发多种DNA损伤反应的初始事件。具体的起始事件可能是原本隐藏的单链3'端突出端(TTAGGG串联重复序列)的暴露,在没有DNA损伤的情况下,外源性提供的T-寡核苷酸可以向细胞提供这个信号。T-寡核苷酸处理引发SOS样反应和/或导致已恶性转化细胞选择性凋亡的能力,可能为癌症预防和治疗提供一种重要的新方法。