Nucleolar DNA Double-Strand Break Responses Underpinning rDNA Genomic Stability

Area of Science:

• Cell Biology
• Genomics
• Molecular Biology

Background:

• Nucleoli are essential for ribosome biogenesis, forming around transcriptionally active ribosomal gene (rDNA) arrays.
• Nucleolar organiser regions (NORs) are prone to DNA damage due to high transcriptional activity.
• Genomic stability of NORs is crucial and protected by specialized cellular responses.

Purpose of the Study:

• To review nucleolar responses to DNA double-strand breaks (DSBs) within rDNA arrays.
• To explore the mechanisms of rDNA DSB repair, including the role of homology-directed repair (HDR).
• To examine how nucleoli sense and respond to DSBs occurring both within and outside rDNA loci.

Main Methods:

• Review of existing literature on nucleolar responses to DNA damage.
• Analysis of studies using sequence-specific endonucleases (e.g., CRISPR/Cas9) to induce DSBs in rDNA.
• Examination of evidence for nucleolar sensing of extranuclear DSBs.

Main Results:

• Homology-directed repair (HDR) is the predominant pathway for repairing rDNA DSBs.
• Inhibition of RNA polymerase-I (Pol-I) transcription and significant nucleolar reorganisation facilitate rDNA repair.
• Nucleoli demonstrate the capacity to detect and respond to DSBs throughout the genome.

Conclusions:

• Nucleoli employ coordinated responses involving transcription inhibition and reorganisation to repair rDNA DSBs via HDR.
• These mechanisms are vital for maintaining the genomic integrity of essential rDNA regions.
• The nucleolus acts as a critical hub for sensing and responding to DNA damage across the genome.