Evolution of coordinated mutagenesis and somatic hypermutation in VH5.

Evolution of coordinated mutagenesis and somatic hypermutation in VH5.
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DOI:
10.1016/j.molimm.2011.10.001
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发表时间:
2011-12
影响因子:
3.6
通讯作者:
Minnick MF
Minnick MF
中科院分区:
医学3区
文献类型:
--
作者:
Wright BE;Schmidt KH;Hunt AT;Reschke DK;Minnick MF

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The VH5 human antibody gene was analyzed using a computer program (mfg) which simulates transcription, to better understand transcription-driven mutagenesis events that occur during “phase 1” of somatic hypermutation. Results show that the great majority of mutations in the non-transcribed strand occur within loops of two predicted high-stability stem-loop structures, termed SLS 14.9 and SLS 13.9. In fact, 89% of the 2,505 mutations reported are within the encoded complementarity-determining region (CDR) and occur in loops of these high-stability structures. In vitro studies were also done and verified the existence of SLS 14.9. Following the formation of SLS 14.9 and SLS 13.9, a sustained period of transcriptional activity occurs within a window size of 60-70 nucleotides. During this period, the stability of these two SLSs does not change, and may provide the substrate for base exchanges and mutagenesis. The data suggest that many mutable bases are exposed simultaneously at pause sites, allowing for coordinated mutagenesis.
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