Back to Search
Start Over
Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation.
- Source :
-
Nature communications [Nat Commun] 2024 Sep 06; Vol. 15 (1), pp. 7797. Date of Electronic Publication: 2024 Sep 06. - Publication Year :
- 2024
-
Abstract
- Ribosomal DNA (rDNA) encodes the ribosomal RNA genes and represents an intrinsically unstable genomic region. However, the underlying mechanisms and implications for genome integrity remain elusive. Here, we use Bloom syndrome (BS), a rare genetic disease characterized by DNA repair defects and hyper-unstable rDNA, as a model to investigate the mechanisms leading to rDNA instability. We find that in Bloom helicase (BLM) proficient cells, the homologous recombination (HR) pathway in rDNA resembles that in nuclear chromatin; it is initiated by resection, replication protein A (RPA) loading and BRCA2-dependent RAD51 filament formation. However, BLM deficiency compromises RPA-loading and BRCA1/2 recruitment to rDNA, but not RAD51 accumulation. RAD51 accumulates at rDNA despite depletion of long-range resection nucleases and rDNA damage results in micronuclei when BLM is absent. In summary, our findings indicate that rDNA is permissive to RAD51 accumulation in the absence of BLM, leading to micronucleation and potentially global genomic instability.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Replication Protein A metabolism
Replication Protein A genetics
Homologous Recombination
Bloom Syndrome genetics
Bloom Syndrome metabolism
BRCA2 Protein metabolism
BRCA2 Protein genetics
BRCA1 Protein metabolism
BRCA1 Protein genetics
DNA Repair
Rad51 Recombinase metabolism
Rad51 Recombinase genetics
DNA, Ribosomal genetics
DNA, Ribosomal metabolism
RecQ Helicases metabolism
RecQ Helicases genetics
Genomic Instability
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39242676
- Full Text :
- https://doi.org/10.1038/s41467-024-52189-6