Abstract
We analyzed the effect of transcribed noncoding RNA centromeric satellites on chromosome segregation in normal human and murine stem and fibrosarcoma cells. The overexpression of different centromeric alphoid DNAs in all cell lines induced a marked increase in chromosome mis-segregation in anaphase. Overexpression of centromeric mouse minor satellite also increased chromosome instability in the murine stem but not in human cells. Analysis of chromosome segregation in vivo showed disturbances in the mitotic progression, which was frequently unresolved. Live cell imaging revealed that overexpression of centromeric satellites resulted in several different chromosomal morphological errors in the cell nuclei. Our findings correlated with other reports that several centromeric noncoding RNAs are detected in different carcinoma cells and their expression resulted in segregation errors. Our study furnishes further insights into a novel source of genomic instability in human and murine cells. It has recently been shown that noncoding centromeric RNAs are present in some form of cancer, and thus, overexpression of several types of centromeric noncoding RNAs may be useful as a specific maker for neoplastic cells.
Highlights
IntroductionRepetitive satellite DNA sequences (alphoid DNA) are essential for centromere formation and function during cell division [1, 2]
Repetitive satellite DNA sequences are essential for centromere formation and function during cell division [1, 2]
We showed that overexpression of centromeric sequences from different suprachromosomal families induced a similar effect on chromosome segregation in both human stem (HUES-10) and fibrosarcoma (HT1080) cells
Summary
Repetitive satellite DNA sequences (alphoid DNA) are essential for centromere formation and function during cell division [1, 2]. The centromere protein (CENP) requirements that affect chromosome function and segregation are complex [3]. Factors such as noncoding RNAs (ncRNAs) formed from transcripts of centromeric satellite DNA influence chromosome and chromatin organisation in human [4] and murine [5, 6] cells. Human centromeric RNAs were found to be transcribed in several tumour types but not in normal somatic tissues, suggesting that ncRNAs may play a role in cancer establishment or progression [7, 8]. In recent years, growing evidence has shown that transcription of noncoding RNA from pericentric and centromeric satellites could lead to mitotic or segregation errors [9]. The dosage balance of the ncRNAs is important for correct cell cycle progression, and balance perturbation might result in malignancy [10]
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