Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination
Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination
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DOI：
10.1073/pnas.241525998
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发表时间：
2001-12-04
影响因子：
11.1
通讯作者：
Neuberger, MS
中科院分区：
文献类型：
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作者：
Ehrenstein, MR;Rada, C;Neuberger, MS
同种型转换涉及一种区域特异性的、非同源重组性缺失，这种缺失被认为是由断裂的DNA末端的非同源连接所导致的。在此，我们发现来自PM52缺陷型小鼠的转换连接点处供体/受体同源性增加，并提出类别转换可通过微同源性介导的末端连接发生。有趣的是，尽管同种型转换和体细胞高频突变显示出许多相似之处，但我们证实PMS2缺陷对体细胞高频突变过程中产生的核苷酸替换模式没有重大影响。这一发现与MSH2缺陷形成对比。对于MSH2，转换重组和高频突变模式的改变表明这两个过程在机制上存在相似之处，而PMS2缺陷仅影响转换重组这一事实可能反映了断裂修复途径的差异。
Isotype switching involves a region-specific, nonhomologous recombinational deletion that has been suggested to occur by nonhomologous joining of broken DNA ends. Here, we find increased donor/acceptor homology at switch junctions from PM52-deficient mice and propose that class switching can occur by microhomology-mediated end-joining. Interestingly, although isotype switching and somatic hypermutation show many parallels, we confirm that PMS2 deficiency has no major effect on the pattern of nucleotide substitutions generated during somatic hypermutation. This finding is in contrast to MSH2 deficiency. With MSH2, the altered pattern of switch recombination and hypermutation suggests parallels in the mechanics of the two processes, whereas the fact that PMS2 deficiency affects only switch recombination may reflect differences in the pathways of break resolution.