| First Author | Hakim O | Year | 2012 |
| Journal | Nature | Volume | 484 |
| Issue | 7392 | Pages | 69-74 |
| PubMed ID | 22314321 | Mgi Jnum | J:183679 |
| Mgi Id | MGI:5319096 | Doi | 10.1038/nature10909 |
| Citation | Hakim O, et al. (2012) DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature 484(7392):69-74 |
| abstractText | Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies. |
