Mutations occur in the Ig Smu region but rarely in Sgamma regions prior to class switch recombination.
EMBO J
; 22(21): 5893-903, 2003 Nov 03.
Article
en En
| MEDLINE
| ID: mdl-14592986
ABSTRACT
Nucleotide substitutions are found in recombined Ig switch (S) regions and also in unrecombined (germline, GL) Smicro segments in activated splenic B cells. Herein we examine whether mutations are also introduced into the downstream acceptor S regions prior to switch recombination, but find very few mutations in GL Sgamma3 and Sgamma1 regions in activated B cells. These data suggest that switch recombination initiates in the Smicro segment and secondarily involves the downstream acceptor S region. Furthermore, the pattern and specificity of mutations in GL and recombined Smicro segments differ, suggesting different repair mechanisms. Mutations in recombined Smicro regions show a strong bias toward G/C base pairs and WRCY/RGYW hotspots, whereas mutations introduced into the GL Smicro do not. Additionally, induction conditions affect mutation specificity within the GL Smicro segment. Mutations are most frequent near the S-S junctions and decrease rapidly with distance from the junction. Finally, we find that mice expressing a transgene for terminal deoxynucleotidyl transferase (TdT) have nucleotide insertions at S-S junctions, indicating that the recombining DNA ends are accessible to end-processing enzyme activities.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Recombinación Genética
/
Región de Cambio de la Inmunoglobulina
/
Proteínas de Unión al ADN
/
Mutación
Límite:
Animals
Idioma:
En
Revista:
EMBO J
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos