Cellular aging is characterized by the loss of DNA replication capability and is mainly brought about by various changes in chromatin structure. Here, we examined changes in MCM2–7 proteins, which act as a replicative DNA helicase, during aging of human WI38 fibroblasts at the single-cell level. We used nuclear accumulation of p21 as a marker of senescent cells, and examined changes in MCM2–7 by western blot analysis. First, we found that senescent cells are enriched for cells with a DNA content higher than 4N. Second, the levels of MCM2, MCM3, MCM4 and MCM6 proteins decreased in senescent cells. Third, cytoplasmic localization of MCM2 and MCM7 was observed in senescent cells, from an analysis of MCM2–7 except for MCM5. Consistent with this finding, fragmented MCM2 was predominant in these cells. These age-dependent changes in MCM2–7, a protein complex that directly affects cellular DNA replication, may play a critical role in cellular senescence.
The majority of eukaryotic genomes contain a large fraction of repetitive sequences that primarily originate from transpositional bursts of transposable elements (TEs). Repbase serves as a database for eukaryotic repetitive sequences and has now become the largest collection of eukaryotic TEs. During the development of Repbase, many new superfamilies/lineages of TEs, which include Helitron, Polinton, Ginger and SINEU, were reported. The unique composition of protein domains and DNA motifs in TEs sometimes indicates novel mechanisms of transposition, replication, anti-suppression or proliferation. In this review, our current understanding regarding the diversity of eukaryotic TEs in sequence, protein domain composition and structural hallmarks is introduced and summarized, based on the classification system implemented in Repbase. Autonomous eukaryotic TEs can be divided into two groups: Class I TEs, also called retrotransposons, and Class II TEs, or DNA transposons. Long terminal repeat (LTR) retrotransposons, including endogenous retroviruses, non-LTR retrotransposons, tyrosine recombinase retrotransposons and Penelope-like elements, are well accepted groups of autonomous retrotransposons. They share reverse transcriptase for replication but are distinct in the catalytic components responsible for integration into the host genome. Similarly, at least three transposition machineries have been reported in eukaryotic DNA transposons: DDD/E transposase, tyrosine recombinase and HUH endonuclease combined with helicase. Among these, TEs with DDD/E transposase are dominant and are classified into 21 superfamilies in Repbase. Non-autonomous TEs are either simple derivatives generated by internal deletion, or are composed of several units that originated independently.