Venkatesan Shriram, Natarajan Adayapalam T, Hande M Prakash
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597.
Department of Ecological and Biological Sciences, University of Tuscia, Viterbo 01100, Italy.
Mutat Res Genet Toxicol Environ Mutagen. 2015 Nov;793:176-84. doi: 10.1016/j.mrgentox.2015.08.008. Epub 2015 Aug 28.
Chromosomal instability is defined as a state of numerical and/or structural chromosomal anomalies in cells. Numerous studies have documented the incidence of chromosomal instability, which acutely or chronically may lead to accelerated ageing (tissue-wide or even organismal), cancer or other genetic disorders. Potential mechanisms leading to the generation of chromosome-genome instability include erroneous/inefficient DNA repair, chromosome segregation defects, spindle assembly defects, DNA replication stress, telomere shortening/dysfunction - to name a few. Understanding the cellular and molecular mechanisms for chromosomal instability in various human cells and tissues will be useful in elucidating the cause for many age associated diseases including cancer. This approach holds a great promise for the cytogenetic assays not only for prognosis but also for diagnostic purposes in clinical settings. In this review, a multi-dimensional approach has been attempted to portray the complexity behind the incidence of chromosome-genome instability including evolutionary implications at the species level for some of the mechanisms of chromosomal instability.
染色体不稳定性被定义为细胞中染色体数量和/或结构异常的一种状态。大量研究记录了染色体不稳定性的发生率，其可能急性或慢性地导致加速衰老（全组织甚至整个生物体）、癌症或其他遗传疾病。导致染色体-基因组不稳定产生的潜在机制包括错误/低效的DNA修复、染色体分离缺陷、纺锤体组装缺陷、DNA复制应激、端粒缩短/功能障碍等等。了解各种人类细胞和组织中染色体不稳定性的细胞和分子机制，将有助于阐明包括癌症在内的许多与年龄相关疾病的病因。这种方法不仅对细胞遗传学检测在临床环境中的预后有很大前景，而且对诊断也有很大前景。在这篇综述中，我们尝试采用一种多维度方法来描绘染色体-基因组不稳定性发生率背后的复杂性，包括在物种水平上对某些染色体不稳定性机制的进化影响。
