Ribonucleotides can be incorporated into DNA during replication by the replicative DNA polymerases. These aberrant DNA subunits are efficiently recognized and removed by Ribonucleotide Excision Repair, which is initiated by the heterotrimeric enzyme RNase H2. While RNase H2 is essential in higher eukaryotes, the yeast Saccharomyces cerevisiae can survive without RNase H2 enzyme, although the genome undergoes mutation, recombination and other genome instability events at an increased rate. Although RNase H2 can be considered as a protector of the genome from the deleterious events that can ensue from recognition and removal of embedded ribonucleotides, under conditions of high ribonucleotide incorporation and retention in the genome in a RNase H2-negative strain, sudden introduction of active RNase H2 causes massive DNA breaks and genome instability in a condition which we term ‘ribodysgenesis’. The DNA breaks and genome instability arise solely from RNase H2 cleavage directed to the ribonucleotide-containing genome. Survivors of ribodysgenesis have massive loss of heterozygosity events stemming from recombinogenic lesions on the ribonucleotide-containing DNA, with increases of over 1000X from wild-type. DNA breaks are produced over one to two divisions and subsequently cells adapt to RNase H2 and ribonucleotides in the genome and grow with normal levels of genome instability.

中文翻译：

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Ribodysgenesis：酵母基因组突然不稳定性酿酒酵母由 RNase H2 裂解引起的基因组嵌入核糖核苷酸

在复制性 DNA 聚合酶的复制过程中，核糖核苷酸可以掺入 DNA。这些异常的 DNA 亚基被异源三聚体酶 RNase H2 启动的核糖核苷酸切除修复有效识别和去除。虽然 RNase H2 在高等真核生物中必不可少，但酿酒酵母可以在没有 RNase H2 酶的情况下存活，尽管基因组以更高的速度经历突变、重组和其他基因组不稳定事件。尽管 RNase H2 可以被认为是基因组的保护者，可以防止识别和去除嵌入的核糖核苷酸引起的有害事件，但在 RNase H2 阴性菌株的基因组中高核糖核苷酸掺入和保留的条件下，活性 RNase H2 的突然引入导致大量 DNA 断裂和基因组不稳定，我们称之为“核糖体发生”。DNA 断裂和基因组不稳定性仅由针对含核糖核苷酸的基因组的 RNase H2 裂解引起。核糖体发生的幸存者由于含有核糖核苷酸的 DNA 上的重组损伤而导致杂合性事件大量丢失，与野生型相比增加了 1000 倍以上。DNA 断裂在一到两个分裂过程中产生，随后细胞适应基因组中的 RNase H2 和核糖核苷酸，并在正常水平的基因组不稳定性下生长。核糖体发生的幸存者由于含有核糖核苷酸的 DNA 上的重组损伤而导致杂合性事件大量丢失，与野生型相比增加了 1000 倍以上。DNA 断裂在一到两个分裂过程中产生，随后细胞适应基因组中的 RNase H2 和核糖核苷酸，并在正常水平的基因组不稳定性下生长。核糖体发生的幸存者由于含有核糖核苷酸的 DNA 上的重组损伤而导致杂合性事件大量丢失，与野生型相比增加了 1000 倍以上。DNA 断裂在一到两个分裂过程中产生，随后细胞适应基因组中的 RNase H2 和核糖核苷酸，并在正常水平的基因组不稳定性下生长。