I. VH gene transcription creates stabilized secondary structures for coordinated mutagenesis during somatic hypermutation.

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 stabl

SUBMITTER: Wright BE 

PROVIDER: S-EPMC2570340 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature