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.

Genome sequencing revealed that nearly half of the human genome is comprised of transposable elements. Although most of these elements have been rendered inactive due to mutations, full-length intact long interspersed element-1 (LINE-1 or L1) copies retain the ability to mobilize through RNA intermediates by a so-called “copy-and-paste” mechanism, termed retrotransposition. L1 is the only known autonomous mobile genetic element in the genome, and its retrotransposition contributes to inter- or intra-individual genetic variation within the human population. However, L1 retrotransposition also poses a threat to genome integrity due to gene disruption and chromosomal instability. Moreover, recent studies suggest that aberrant L1 expression can impact human health by causing diseases such as cancer and chronic inflammation that might lead to autoimmune disorders. To counteract these adverse effects, the host cells have evolved multiple layers of defense mechanisms at the epigenetic, RNA and protein levels. Intriguingly, several host factors have also been reported to facilitate L1 retrotransposition, suggesting that there is competition between negative and positive regulation of L1 by host factors. Here, we summarize the known host proteins that regulate L1 activity at different stages of the replication cycle and discuss how these factors modulate disease-associated phenotypes caused by L1.

Eukaryotic cells contain multiple types of duplicated sequences. Typical examples are tandem repeat sequences including telomeres, centromeres, rDNA genes and transposable elements. Most of these sequences are unstable; thus, their copy numbers or sequences change rapidly in the course of evolution. In this review, I will describe roles of subtelomere regions, which are located adjacent to telomeres at chromosome ends, and recent discoveries about their sequence variation.