Steele Edward J
Mol Immunol. 2008 May;45(10):2723-6. doi: 10.1016/j.molimm.2008.02.002. Epub 2008 Mar 21.
Somatic hypermutation (SHM) of rearranged variable genes proceeds in two phases. Phase I which is well understood is triggered by activation-induced cytidine deaminase (AID) and targets mutations at C:G base pairs equally on both DNA strands. Phase II, is less well understood, and targets A:T base pairs by co-opting DNA polymerase-eta and acts in a strand biased fashion such that mutations off A exceed mutations of T by two- to threefold. Current molecular models attempting to explain A:T targeted Phase II are critically reviewed. It is the author's viewpoint that the 'RT-model', which invokes both transcription-coupled DNA and RNA deamination together with error-prone reverse transcription via Pol-eta, is the best explanation of current somatic hypermutation data.
重排可变基因的体细胞高频突变（SHM）分两个阶段进行。第一阶段已得到充分理解，由激活诱导的胞苷脱氨酶（AID）触发，对两条DNA链上的C:G碱基对进行同等靶向突变。第二阶段的了解较少，它通过协同DNA聚合酶η靶向A:T碱基对，并以链偏向的方式起作用，使得A位点的突变比T位点的突变多两到三倍。对目前试图解释A:T靶向第二阶段的分子模型进行了批判性综述。作者认为，“RT模型”，即同时涉及转录偶联的DNA和RNA脱氨以及通过Pol-η进行的易错逆转录，是目前体细胞高频突变数据的最佳解释。
