Laboratory of Genome Regeneration, Institute for Quantitative Biosciences (IQB), The University of Tokyo.
Department of Biological Sciences, Graduate School of Science, The University of Tokyo.
Genes Genet Syst. 2023 Sep 30;98(3):103-119. doi: 10.1266/ggs.22-00046. Epub 2022 Aug 4.
Organisms have evolved elaborate mechanisms that maintain genome stability. Deficiencies in these mechanisms result in changes to the nucleotide sequence as well as copy number and structural variations in the genome. Genome instability has been implicated in numerous human diseases. However, genomic alterations can also be beneficial as they are an essential part of the evolutionary process. Organisms sometimes program genomic changes that drive genetic and phenotypic diversity. Therefore, genome alterations can have both positive and negative impacts on cellular growth and functions, which underscores the need to control the processes that restrict or induce such changes to the genome. The ribosomal RNA gene (rDNA) is highly abundant in eukaryotic genomes, forming a cluster where numerous rDNA copies are tandemly arrayed. Budding yeast can alter the stability of its rDNA cluster by changing the rDNA copy number within the cluster or by producing extrachromosomal rDNA circles. Here, we review the mechanisms that regulate the stability of the budding yeast rDNA cluster during repair of DNA double-strand breaks that are formed in response to programmed DNA replication fork arrest.
生物已经进化出了复杂的机制来维持基因组的稳定性。这些机制的缺陷会导致核苷酸序列以及基因组的拷贝数和结构发生变化。基因组不稳定性与许多人类疾病有关。然而，基因组的改变也可能是有益的，因为它们是进化过程的重要组成部分。生物有时会对基因组进行编程，从而驱动基因和表型的多样性。因此，基因组的改变可能对细胞的生长和功能产生积极和消极的影响，这突显了控制限制或诱导基因组发生此类改变的过程的必要性。核糖体 RNA 基因（rDNA）在真核生物基因组中含量丰富，形成一个簇，其中许多 rDNA 拷贝串联排列。芽殖酵母可以通过改变簇内的 rDNA 拷贝数或产生染色体外 rDNA 环来改变其 rDNA 簇的稳定性。在这里，我们综述了在响应有丝分裂过程中 DNA 复制叉阻滞而形成的 DNA 双链断裂修复过程中，调节芽殖酵母 rDNA 簇稳定性的机制。
