DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes

Article

关键词: CLASS-SWITCH RECOMBINATION;    SEQUENCING REVEALS;    HUMAN GENOME;    BREAKS;    CELLS;    AID;    IDENTIFICATION;    REARRANGEMENTS;    ORGANIZATION;    MECHANISMS;   

DOI  :  10.1038/nature10909

来源: SCIE

【 摘 要 】

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.

【 授权许可】

Free