Deoxyuridine triphosphate incorporation during somatic hypermutation of mouse VkOx genes after immunization with phenyloxazolone.
J Immunol
; 185(8): 4777-82, 2010 Oct 15.
Article
de En
| MEDLINE
| ID: mdl-20861355
ABSTRACT
Somatic hypermutation (SHM) of Ig genes is the result of a two-phase process initiated by activation-induced cytidine deaminase, relying on two different strategies for the introduction of mutations at CG pairs (phase I) and at AT pairs (phase II). To explain the selectivity of phase II, two mechanisms were proposed AT-selective error-prone DNA-polymerases, deoxyuridine triphosphate (dUTP) incorporation, or both. However, there has been no experimental evidence so far of the possible involvement of the latter. We have developed a ligation-anchored PCR method based on the formation of single-strand breaks at uracils. In this study, we show the presence of uracil in hypermutating VkOx genes in wild type (AID(+/+)) mice, demonstrating that dUTP incorporation via DNA polymerases could be a major mechanism in SHM. Thus, error-prone DNA polymerases would participate in SHM via low-fidelity replication and incorporation of dUTP.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Gènes d'immunoglobuline
/
4-Éthoxyméthylène-2-phényl-oxazol-5(4H)-one
/
Hypermutation somatique des gènes des immunoglobulines
/
Nucléotides désoxyuridyliques
Limites:
Animals
Langue:
En
Journal:
J Immunol
Année:
2010
Type de document:
Article
Pays d'affiliation:
France