Nucleolar DNA Double-Strand Break Responses Underpinning rDNA Genomic Stability

Publication date: Available online 25 July 2019Source: Trends in GeneticsAuthor(s): Marjolein van Sluis, Brian McStayNucleoli, the sites of ribosome biogenesis, form around ribosomal gene (rDNA) arrays termed nucleolar organiser regions (NORs). These are the most transcriptionally active regions of the human genome and specialised responses have evolved to ensure their genomic stability. This review focuses on nucleolar responses to DNA double-strand breaks (DSBs) introduced into rDNA arrays using sequence-specific endonucleases, including CRISPR/Cas9. Repair of rDNA DSBs is predominantly carried out by the homology-directed repair (HDR) pathway that is facilitated by inhibition of transcription by RNA polymerase-I (Pol-I) and ensuing dramatic nucleolar reorganisation. Additionally, we review evidence that nucleoli can sense and respond to DSBs elsewhere in the genome.
Source: Trends in Genetics - Category: Genetics & Stem Cells Source Type: research