Long Neural Genes Harbor Recurrent DNA Break Clusters in Neural Stem/Progenitor Cells.
Cell
; 164(4): 644-55, 2016 Feb 11.
Article
in En
| MEDLINE
| ID: mdl-26871630
ABSTRACT
Repair of DNA double-strand breaks (DSBs) by non-homologous end joining is critical for neural development, and brain cells frequently contain somatic genomic variations that might involve DSB intermediates. We now use an unbiased, high-throughput approach to identify genomic regions harboring recurrent DSBs in primary neural stem/progenitor cells (NSPCs). We identify 27 recurrent DSB clusters (RDCs), and remarkably, all occur within gene bodies. Most of these NSPC RDCs were detected only upon mild, aphidicolin-induced replication stress, providing a nucleotide-resolution view of replication-associated genomic fragile sites. The vast majority of RDCs occur in long, transcribed, and late-replicating genes. Moreover, almost 90% of identified RDC-containing genes are involved in synapse function and/or neural cell adhesion, with a substantial fraction also implicated in tumor suppression and/or mental disorders. Our characterization of NSPC RDCs reveals a basis of gene fragility and suggests potential impacts of DNA breaks on neurodevelopment and neural functions.
Full text:
1
Database:
MEDLINE
Main subject:
DNA Breaks
/
Neural Stem Cells
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell
Year:
2016
Type:
Article
Affiliation country:
United States