Usdin Karen, House Nealia C M, Freudenreich Catherine H
Laboratory of Cell and Molecular Biology, NIDDK, NIH , Bethesda, MD , USA .
Crit Rev Biochem Mol Biol. 2015 Mar-Apr;50(2):142-67. doi: 10.3109/10409238.2014.999192. Epub 2015 Jan 22.
The expansion of repeated sequences is the cause of over 30 inherited genetic diseases, including Huntington disease, myotonic dystrophy (types 1 and 2), fragile X syndrome, many spinocerebellar ataxias, and some cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat expansions are dynamic, and disease inheritance and progression are influenced by the size and the rate of expansion. Thus, an understanding of the various cellular mechanisms that cooperate to control or promote repeat expansions is of interest to human health. In addition, the study of repeat expansion and contraction mechanisms has provided insight into how repair pathways operate in the context of structure-forming DNA, as well as insights into non-canonical roles for repair proteins. Here we review the mechanisms of repeat instability, with a special emphasis on the knowledge gained from the various model systems that have been developed to study this topic. We cover the repair pathways and proteins that operate to maintain genome stability, or in some cases cause instability, and the cross-talk and interactions between them.
重复序列的扩增是30多种遗传性疾病的病因，包括亨廷顿病、强直性肌营养不良（1型和2型）、脆性X综合征、多种脊髓小脑共济失调，以及一些肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）病例。重复序列扩增具有动态性，疾病的遗传和进展受扩增大小和速率的影响。因此，了解协同控制或促进重复序列扩增的各种细胞机制对人类健康具有重要意义。此外，对重复序列扩增和收缩机制的研究为了解修复途径在形成结构的DNA背景下如何运作提供了线索，也为修复蛋白的非经典作用提供了见解。在此，我们综述重复序列不稳定性的机制，特别强调从为研究该主题而开发的各种模型系统中获得的知识。我们涵盖了为维持基因组稳定性而发挥作用或在某些情况下导致不稳定性的修复途径和蛋白质，以及它们之间的相互作用和相互影响。
