| First Author | Barlow JH | Year | 2013 |
| Journal | Cell | Volume | 152 |
| Issue | 3 | Pages | 620-32 |
| PubMed ID | 23352430 | Mgi Jnum | J:193481 |
| Mgi Id | MGI:5468605 | Doi | 10.1016/j.cell.2013.01.006 |
| Citation | Barlow JH, et al. (2013) Identification of Early Replicating Fragile Sites that Contribute to Genome Instability. Cell 152(3):620-32 |
| abstractText | DNA double-strand breaks (DSBs) in B lymphocytes arise stochastically during replication or as a result of targeted DNA damage by activation-induced cytidine deaminase (AID). Here we identify recurrent, early replicating, and AID-independent DNA lesions, termed early replication fragile sites (ERFSs), by genome-wide localization of DNA repair proteins in B cells subjected to replication stress. ERFSs colocalize with highly expressed gene clusters and are enriched for repetitive elements and CpG dinucleotides. Although distinct from late-replicating common fragile sites (CFS), the stability of ERFSs and CFSs is similarly dependent on the replication-stress response kinase ATR. ERFSs break spontaneously during replication, but their fragility is increased by hydroxyurea, ATR inhibition, or deregulated c-Myc expression. Moreover, greater than 50% of recurrent amplifications/deletions in human diffuse large B cell lymphoma map to ERFSs. In summary, we have identified a source of spontaneous DNA lesions that drives instability at preferred genomic sites. |
