I. VH gene transcription creates stabilized secondary structures for coordinated mutagenesis during somatic hypermutation.
Mol Immunol
; 45(13): 3589-99, 2008 Aug.
Article
em En
| MEDLINE
| ID: mdl-18585784
ABSTRACT
During the adaptive immune response, antigen challenge triggers a million-fold increase in mutation rates in the variable-region antibody genes. The frequency of mutation is causally and directly linked to transcription, which provides ssDNA and drives supercoiling that stabilizes secondary structures containing unpaired, intrinsically mutable bases. Simulation analysis of transcription in VH5 reveals a dominant 65nt secondary structure in the non-transcribed strand containing six sites of mutable ssDNA that have also been identified independently in human B cell lines and in primary mouse B cells. This dominant structure inter-converts briefly with less stable structures and is formed repeatedly during transcription, due to periodic pauses and backtracking. In effect, this creates a stable yet dynamic "mutability platform" consisting of ever-changing patterns of unpaired bases that are simultaneously exposed and therefore able to coordinate mutagenesis. Such a complex of secondary structures may be the source of ssDNA for enzyme-based diversification, which ultimately results in high affinity antibodies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Mutagênese
/
Hipermutação Somática de Imunoglobulina
/
Genes de Cadeia Pesada de Imunoglobulina
/
Conformação de Ácido Nucleico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos