Abstract
The pericentric satellite III (SatIII or Sat3) and II tandem repeats recently appeared to be transcribed under stress conditions, and the transcripts were shown to play an essential role in the universal stress response. In this paper, we review the role of human-specific SatIII copy number variation (CNV) in normal stress response, aging and pathology, with a focus on 1q12 loci. We postulate a close link between transcription of SatII/III repeats and their CNV. The accrued body of data suggests a hypothetical universal mechanism, which provides for SatIII copy gain during the stress response, alongside with another, more hypothetical reverse mechanism that might reduce the mean SatIII copy number, likely via the selection of cells with excessively large 1q12 loci. Both mechanisms, working alternatively like swings of the pendulum, may ensure the balance of SatIII copy numbers and optimum stress resistance. This model is verified on the most recent data on SatIII CNV in pathology and therapy, aging, senescence and response to genotoxic stress in vitro.
Highlights
The global stress response, in addition to human skin fibroblast (HSF) inducible gene transcriptional stimulation, which is beyond this review, is composed of global transcriptional repression, modulating splicing activities, and HSF-independent transcriptional de-repression of genes located in the vicinity of nuclear stress bodies
SatIII-dependent Nuclear Stress Bodies (nSBs) serve as a conditional platform for phosphorylation of SRSFs by CDC-like kinase 1 (CLK1) to promote the rapid adaptation of gene expression through intron retention (IR) following thermal stress exposure [66]
Summarizing, we propose a universal mechanism to launch a process of augmentation of SatIII (1q12) and other pericentric tandem repeat copy numbers in chronic stress (Chernobyl zone), replicative senescence, normal and accelerated aging and various cancers
Summary
The transcription of satellite DNA has been reported in different biological contexts [11,33,34], including development [22,35,36,37], cell cycle [22,34] and cellular response to stress [33,37,38,39], the latter being a general adaptive reaction in human cells [23]. An amazing link to the stress reaction is well established for the satellite DNA transcription
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