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.
journal_name
Celljournal_title
Cellauthors
Wei PC,Chang AN,Kao J,Du Z,Meyers RM,Alt FW,Schwer Bdoi
10.1016/j.cell.2015.12.039subject
Has Abstractpub_date
2016-02-11 00:00:00pages
644-55issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(15)01703-1journal_volume
164pub_type
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