DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes.
Nature
; 484(7392): 69-74, 2012 Feb 07.
Article
em En
| MEDLINE
| ID: mdl-22314321
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Translocação Genética
/
Dano ao DNA
/
Linfócitos B
Limite:
Animals
Idioma:
En
Revista:
Nature
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos