Tandemly repeated satellite DNAs are major components of centromeres and pericentromeric heterochromatin which are crucial chromosomal elements responsible for accurate chromosome segregation. Satellite DNAs also contribute to genome evolution and the speciation process and are important for the maintenance of the entire genome inside the nucleus. In addition, there is increasing evidence for active and tightly regulated transcription of satellite DNAs and for the role of their transcripts in diverse processes. In this review, we focus on recent discoveries related to the regulation of satellite DNA expression and the role of their transcripts, either in heterochromatin establishment and centromere function or in gene expression regulation under various biological contexts. We discuss the role of satellite transcripts in the stress response and environmental adaptation as well as consequences of the dysregulation of satellite DNA expression in cancer and their potential use as cancer biomarkers.
The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker.
Bacterial SSB proteins, as well as their eukaryotic RPA analogues, are essential and ubiquitous. They avidly bind single-stranded DNA and regulate/coordinate its metabolism, hence enabling essential DNA processes such as replication, transcription, and repair. The prototypic Escherichia coli SSB protein is encoded by an ssb gene. Although the ssb gene promoters harbor an SOS box, multiple studies over several decades failed to elucidate whether ssb gene expression is inducible and SOS dependent. The SOS regulon is comprised of about 50 genes, whose transcription is coordinately induced under stress conditions. Using quantitative real-time PCR, we determined the ssb gene expression kinetics in UV- and γ-irradiated E. coli and revealed that ssb gene expression is elevated in irradiated cells in an SOS-dependent manner. Additionally, the expression of the sulA gene was determined to indicate the extent of SOS induction. In a mutant with a constitutively induced SOS regulon, the ssb gene was overexpressed in the absence of DNA damage. Furthermore, we measured ssb gene expression by droplet digital PCR during unaffected bacterial growth and revealed that ssb gene expression was equal in wild-type and SOS− bacteria, whereas sulA expression was higher in the former. This study thus reveals a complex pattern of ssb gene expression, which under stress conditions depends on the SOS regulon, whereas during normal bacterial growth it is unlinked to SOS induction. The E. coli ssb gene is SOS regulated in such a way that its basal expression is relatively high and can be increased only through stronger SOS induction. The remarkable SOS induction observed in undisturbed wild-type cells may challenge our notion of the physiological role of the SOS response in bacteria.
Bladder cancer (BC) is a common urological malignancy that lacks the non-invasive biomarkers that would make it suitable for early diagnosis. Human alpha-satellite DNA (hASAT) is a tandemly repeated centromeric/pericentromeric DNA family associated with chromosomal stability and cancer-related genomic instability. We quantified extracellular hASAT (ec-hASAT) in plasma circulating cell-free DNA by nanoplate-based digital PCR in a pilot cohort including 29 BC-negative samples, 10 patients with non-muscle-invasive BC (NMIBC), and 7 patients with muscle-invasive BC (MIBC). Plasma ec-hASAT copy number was higher in patients with BC than in the BC-negative group (Mann–Whitney U test, p = 6.61 × 10−7). BC-negative samples ranged from 225 to 11,864 copies/µL plasma, whereas BC samples ranged from 1138 to 16,097 copies/µL plasma. ROC analysis yielded an AUC of 0.944 for discriminating BC from BC-negative samples. At an exploratory threshold of 2000 copies/µL plasma, sensitivity was 94.1% (16/17; exact 95% CI, 71.3–99.9%) and specificity was 89.7% (26/29; exact 95% CI, 72.6–97.8%). These preliminary data support plasma ec-hASAT as a candidate minimally invasive biomarker for BC detection, including NMIBC, and justify validation in larger prospective cohorts.