Genome Instability Induced by Low Levels of Replicative DNA Polymerases in Yeast.

Genome Instability Induced by Low Levels of Replicative DNA Polymerases in Yeast.
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基因组不稳定性由酵母中低水平的复制性DNA聚合酶诱导。

DOI:
10.3390/genes9110539
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发表时间:
2018-11-07
期刊:
影响因子:
3.5
通讯作者:
Petes TD
Petes TD
中科院分区:
生物学3区
文献类型:
--
作者:
Zheng DQ;Petes TD

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实体瘤的大多数细胞具有非常高水平的几种不同类型的基因组不稳定性,包括缺失、复制、易位和非整倍性。这种不稳定性大部分是由DNA复制应激引起的。作为理解这种类型的不稳定性的模型,我们研究了酵母菌株中基因组的不稳定性,这些酵母菌株具有低水平的两种复制型DNA聚合酶:DNA聚合酶α和DNA聚合酶δ(Polα和Polδ)。我们发现,低水平的这些DNA聚合酶中的任何一种都会导致有丝分裂重组,染色体重排和缺失/重复的水平大大提高。然而,两种类型菌株的事件谱在许多方面不同。例如,Polδ水平降低会使单碱基改变和小的缺失显著高于Polα水平降低。在这篇综述中,我们将总结用于监测酵母基因组不稳定性的方法,以及这种分析如何有助于理解基因组不稳定性和DNA复制应激之间的联系。
Most cells of solid tumors have very high levels of genome instability of several different types, including deletions, duplications, translocations, and aneuploidy. Much of this instability appears induced by DNA replication stress. As a model for understanding this type of instability, we have examined genome instability in yeast strains that have low levels of two of the replicative DNA polymerases: DNA polymerase α and DNA polymerase δ (Polα and Polδ). We show that low levels of either of these DNA polymerases results in greatly elevated levels of mitotic recombination, chromosome rearrangements, and deletions/duplications. The spectrum of events in the two types of strains, however, differs in a variety of ways. For example, a reduced level of Polδ elevates single-base alterations and small deletions considerably more than a reduced level of Polα. In this review, we will summarize the methods used to monitor genome instability in yeast, and how this analysis contributes to understanding the linkage between genome instability and DNA replication stress.
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