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Ciliogenesis and the DNA damage response: a stressful relationship

机译：睫毛发生与DNA损伤反应：压力关系

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Both inherited and sporadic mutations can give rise to a plethora of human diseases. Through myriad diverse cellular processes, sporadic mutations can arise through a failure to accurately replicate the genetic code or by inaccurate separation of duplicated chromosomes into daughter cells. The human genome has therefore evolved to encode a large number of proteins that work together with regulators of the cell cycle to ensure that it remains error-free. This is collectively known as the DNA damage response (DDR), and genome stability mechanisms involve a complex network of signalling and processing factors that ensure redundancy and adaptability of these systems. The importance of genome stability mechanisms is best illustrated by the dramatic increased risk of cancer in individuals with underlying disruption to genome maintenance mechanisms. Cilia are microtubule-based sensory organelles present on most vertebrate cells, where they facilitate transduction of external signals into the cell. When not embedded within the specialised ciliary membrane, components of the primary cilium’s basal body help form the microtubule organising centre that controls cellular trafficking and the mitotic segregation of chromosomes. Ciliopathies are a collection of diseases associated with functional disruption to cilia function through a variety of different mechanisms. Ciliopathy phenotypes can vary widely, and although some cellular overgrowth phenotypes are prevalent in a subset of ciliopathies, an increased risk of cancer is not noted as a clinical feature. However, recent studies have identified surprising genetic and functional links between cilia-associated proteins and genome maintenance factors. The purpose of this mini-review is to therefore highlight some of these discoveries and discuss their implications with regards to functional crosstalk between the DDR and ciliogenesis pathways, and how this may impact on the development of human disease.
机译：遗传突变和偶发突变均可引起多种人类疾病。通过无数种多样的细胞过程，零星的突变可能是由于无法准确复制遗传密码或由于将重复的染色体错误地分离到子细胞中而引起的。因此，人类基因组已进化为编码大量蛋白质，这些蛋白质可与细胞周期的调节剂协同工作，以确保其保持无错误。这被统称为DNA损伤反应（DDR），而基因组稳定机制涉及复杂的信号和处理因子网络，这些网络可确保这些系统的冗余性和适应性。基因组稳定机制的重要性可以通过对基因组维持机制有潜在破坏的个体患癌症的风险急剧增加而得到最好的说明。纤毛是存在于大多数脊椎动物细胞中的基于微管的感觉细胞器，它们促进外部信号向细胞内的传导。当未嵌入特殊的睫状膜内时，初级纤毛的基体成分将帮助形成控制细胞运输和染色体有丝分裂分离的微管组织中心。小肠病是通过各种不同的机制与纤毛功能破坏相关的疾病的集合。睫状体疾病表型可以广泛地变化，尽管某些细胞过度生长表型在一系列的纤毛病中很普遍，但是临床上并未发现患癌的风险增加。然而，最近的研究发现纤毛相关蛋白与基因组维持因子之间令人惊讶的遗传和功能联系。因此，本微型审查的目的是强调其中一些发现，并讨论它们与DDR和纤毛生成途径之间的功能性串扰有关的含义，以及这可能如何影响人类疾病的发展。

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