Human rDNA and Cancer

In human cells, each rDNA unit consists of the ~13 kb long ribosomal part and ~30 kb long intergenic spacer (IGS). The ribosomal part, transcribed by RNA polymerase I (pol I), includes genes coding for 18S, 5.8S, and 28S RNAs of the ribosomal particles, as well as their four transcribed spacers. Bei...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2021-12, Vol.10 (12), p.3452
Main Authors: Smirnov, Evgeny, Chmúrčiaková, Nikola, Cmarko, Dušan
Format: Article
Language:English
Subjects:
Binding sites
Biosynthesis
cancer
Cancer therapies
Carcinogenesis
Cell cycle
Cell growth
copy number
DNA damage
DNA methylation
DNA, Intergenic - genetics
DNA, Ribosomal - genetics
DNA-directed RNA polymerase
Gene expression
Genetic transformation
Genetic Variation - genetics
Genomes
human rDNA
Humans
IGS
Mutation - genetics
Neoplasms - genetics
Neoplasms - pathology
non-coding RNA
Phenotypes
Proteins
Review
Ribosomal DNA
ribosomal genes
Ribosomes - genetics
RNA polymerase
RNA, Untranslated - genetics
rRNA
Transcription
Transcription factors
Tumors
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Summary:In human cells, each rDNA unit consists of the ~13 kb long ribosomal part and ~30 kb long intergenic spacer (IGS). The ribosomal part, transcribed by RNA polymerase I (pol I), includes genes coding for 18S, 5.8S, and 28S RNAs of the ribosomal particles, as well as their four transcribed spacers. Being highly repetitive, intensively transcribed, and abundantly methylated, rDNA is a very fragile site of the genome, with high risk of instability leading to cancer. Multiple small mutations, considerable expansion or contraction of the rDNA locus, and abnormally enhanced pol I transcription are usual symptoms of transformation. Recently it was found that both IGS and the ribosomal part of the locus contain many functional/potentially functional regions producing non-coding RNAs, which participate in the pol I activity regulation, stress reactions, and development of the malignant phenotype. Thus, there are solid reasons to believe that rDNA locus plays crucial role in carcinogenesis. In this review we discuss the data concerning the human rDNA and its closely associated factors as both targets and drivers of the pathways essential for carcinogenesis. We also examine whether variability in the structure of the locus may be blamed for the malignant transformation. Additionally, we consider the prospects of therapy focused on the activity of rDNA.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10123452