| First Author | Harrigan JA | Year | 2011 |
| Journal | J Cell Biol | Volume | 193 |
| Issue | 1 | Pages | 97-108 |
| PubMed ID | 21444690 | Mgi Jnum | J:177013 |
| Mgi Id | MGI:5293298 | Doi | 10.1083/jcb.201011083 |
| Citation | Harrigan JA, et al. (2011) Replication stress induces 53BP1-containing OPT domains in G1 cells. J Cell Biol 193(1):97-108 |
| abstractText | Chromosomal deletions and rearrangements in tumors are often associated with common fragile sites, which are specific genomic loci prone to gaps and breaks in metaphase chromosomes. Common fragile sites appear to arise through incomplete DNA replication because they are induced after partial replication inhibition by agents such as aphidicolin. Here, we show that in G1 cells, large nuclear bodies arise that contain p53 binding protein 1 (53BP1), phosphorylated H2AX (gammaH2AX), and mediator of DNA damage checkpoint 1 (MDC1), as well as components of previously characterized OPT (Oct-1, PTF, transcription) domains. Notably, we find that incubating cells with low aphidicolin doses increases the incidence and number of 53BP1-OPT domains in G1 cells, and by chromatin immunoprecipitation and massively parallel sequencing analysis of gammaH2AX, we demonstrate that OPT domains are enriched at common fragile sites. These findings invoke a model wherein incomplete DNA synthesis during S phase leads to a DNA damage response and formation of 53BP1-OPT domains in the subsequent G1. |
