Franklin Andrew, Blanden Robert V
The Immune Disease Institute, The Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Trends Immunol. 2008 Apr;29(4):167-72. doi: 10.1016/j.it.2008.01.008. Epub 2008 Mar 7.
Somatic hypermutation has two phases: phase 1 affects cytosine-guanine (C/G) pairs and is triggered by the deamination of cytosine residues in DNA to uracil; phase 2 affects mostly adenine-thymine (A/T) pairs and is induced by the detection of uracil lesions in DNA. It is not known how, at V(D)J genes in mice, hypermutations accumulate at A/T pairs with strand bias without perturbing the strand unbiased accumulation of hypermutations at C/G pairs. Additionally, it is not known why, in contrast, at switch regions in mice, both C/G-targeted and A/T-targeted hypermutations accumulate in a strand unbiased manner. To explain the strand bias paradox, we propose that phase 1 and phase 2 hypermutations are generated at different stages of the cell cycle.
第一阶段影响胞嘧啶 - 鸟嘌呤（C/G）对，由DNA中胞嘧啶残基脱氨形成尿嘧啶触发；第二阶段主要影响腺嘌呤 - 胸腺嘧啶（A/T）对，由检测到DNA中的尿嘧啶损伤诱导。目前尚不清楚在小鼠的V(D)J基因中，高频突变如何在具有链偏向性的A/T对上积累，而不干扰在C/G对上无链偏向性的高频突变积累。此外，与此相反的是，目前尚不清楚为什么在小鼠的转换区，针对C/G和针对A/T的高频突变都以无链偏向的方式积累。为了解释链偏向性悖论，我们提出第一阶段和第二阶段的高频突变是在细胞周期的不同阶段产生的。
