Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Cancer Sci. 2013 Jul;104(7):790-4. doi: 10.1111/cas.12165. Epub 2013 May 12.
Genetic instability is the driving force of the malignant progression of cancer cells. Recently, replication stress has attracted much attention as a source of genetic instability that gives rise to an accumulation of mutations during the lifespan of individuals. However, the molecular details of the process are not fully understood. Here, recent progress in understanding how genetic alterations accumulate at telomeres will be reviewed. In particular, two aspects of telomere replication will be discussed in this context, covering conventional semi-conservative replication, and DNA synthesis by telomerase plus the C-strand fill-in reactions. Although these processes are seemingly telomere-specific, I will emphasize the possibility that the molecular understanding of the telomere events may shed light on genetic instability at other genetic loci in general.
遗传不稳定性是癌细胞恶性进展的驱动力。最近，复制应激作为遗传不稳定性的来源引起了人们的关注，它会导致个体寿命期间突变的积累。然而，这一过程的分子细节尚不完全清楚。本文将综述近年来人们对端粒处遗传改变如何积累的理解进展。特别地，本文将从两个方面讨论端粒复制，包括传统的半保留复制，以及端粒酶加 C 链填补反应的 DNA 合成。尽管这些过程看似是端粒特有的，但我将强调这样一种可能性，即对端粒事件的分子理解可能会普遍揭示其他遗传位点的遗传不稳定性。
