Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon
Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon
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DOI：
10.15698/mic2016.06.506
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发表时间：
2016-06-01
期刊：
影响因子：
4.6
通讯作者：
Klein, Hannah L.
中科院分区：
文献类型：
--
作者：
Epshtein, Anastasiya;Potenski, Catherine J.;Klein, Hannah L.
由于DNA聚合酶的插入、冈崎片段引物的去除失败、可以引发复制的R环以及RNA/cDNA介导的重组，核糖核苷酸可以嵌入DNA中。RNA：DNA杂合体通过RNase H酶去除。DNA中的单个rNMP被RNase H2去除，如果它们保留在前导链上，则可能导致Top1依赖性途径中的诱变。DNA中的rNMP还可以刺激基因组不稳定性，其中包括同源重组基因转换事件。我们以前发现，类似于rNMP刺激的诱变，rNMP刺激的重组也是Top1依赖的。然而，与诱变相反，我们在这里报告说，重组是不刺激rNMPs的复制聚合酶的掺入。相反，重组似乎是由多个连续的rNMP刺激，这可能是由R环或复制引发事件。
Ribonucleotides can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. RNA: DNA hybrids are removed by RNase H enzymes. Single rNMPs in DNA are removed by RNase H2 and if they remain on the leading strand, can lead to mutagenesis in a Top1-dependent pathway. rNMPs in DNA can also stimulate genome instability, among which are homologous recombination gene conversion events. We previously found that, similar to the rNMP-stimulated mutagenesis, rNMP-stimulated recombination was also Top1-dependent. However, in contrast to mutagenesis, we report here that recombination is not stimulated by rNMPs incorporated by the replicative polymerase epsilon. Instead, recombination seems to be stimulated by multiple contiguous rNMPs, which may arise from R-loops or replication priming events.