Zhou Z H, Akgūn E, Jasin M
Cell Biology Program, Sloan-Kettering Institute and Cornell University Graduate School of Medical Sciences, 1275 York Avenue, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8326-33. doi: 10.1073/pnas.151008498.
Genetic instability can be induced by unusual DNA structures and sequence repeats. We have previously demonstrated that a large palindrome in the mouse germ line derived from transgene integration is extremely unstable and undergoes stabilizing rearrangements at high frequency, often through deletions that produce asymmetry. We have now characterized other palindrome rearrangements that arise from complex homologous recombination events. The structure of the recombinants is consistent with homologous recombination occurring by a noncrossover gene conversion mechanism in which a break induced in the palindrome promotes homologous strand invasion and repair synthesis, similar to mitotic break repair events reported in mammalian cells. Some of the homologous recombination events led to expansion in the size of the palindromic locus, which in the extreme case more than doubled the number of repeats. These results may have implications for instability observed at naturally occurring palindromic or quasipalindromic sequences.
遗传不稳定性可由异常的DNA结构和序列重复诱导产生。我们之前已经证明，小鼠生殖系中源自转基因整合的一个大回文序列极其不稳定，并且经常通过产生不对称性的缺失高频发生稳定重排。我们现在已经对由复杂同源重组事件产生的其他回文重排进行了表征。重组体的结构与通过非交叉基因转换机制发生的同源重组一致，在该机制中，回文序列中诱导的断裂促进同源链入侵和修复合成，类似于哺乳动物细胞中报道的有丝分裂断裂修复事件。一些同源重组事件导致回文位点大小增加，在极端情况下，重复次数增加了一倍多。这些结果可能对在天然存在的回文或准回文序列处观察到的不稳定性具有启示意义。
