Ribodysgenesis: sudden genome instability in the yeast Saccharomyces cerevisiae arising from RNase H2 cleavage at genomic-embedded ribonucleotides.
Ribodysgenesis: sudden genome instability in the yeast Saccharomyces cerevisiae arising from RNase H2 cleavage at genomic-embedded ribonucleotides.
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DOI：
10.1093/nar/gkac536
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发表时间：
2022-07-08
影响因子：
14.9
通讯作者：
Klein, Hannah L.
中科院分区：
文献类型：
--
作者：
Sui, Yang;Epstein, Anastasiya;Dominska, Margaret;Zheng, Dao-Qiong;Petes, Thomas D.;Klein, Hannah L.
核糖核苷酸可以在复制过程中通过复制 DNA 聚合酶掺入 DNA 中。这些异常的 DNA 亚基可被核糖核苷酸切除修复有效识别并去除，该修复由异源三聚酶 RNase H2 启动。虽然 RNase H2 在高等真核生物中至关重要，但酿酒酵母在没有 RNase H2 酶的情况下也能生存，尽管基因组会以更高的速度经历突变、重组和其他基因组不稳定事件。虽然 RNase H2 可以被认为是基因组的保护者，免受因识别和去除嵌入的核糖核苷酸而产生的有害事件的影响，但在 RNase H2 阴性菌株的基因组中大量核糖核苷酸掺入和保留的条件下，突然引入活性 RNase H2 会导致大量 DNA 断裂和基因组不稳定，这种情况我们称之为“核糖体发生”。 DNA 断裂和基因组不稳定仅由 RNase H2 对含有核糖核苷酸的基因组进行切割引起。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的大量丧失，与野生型相比增加了1000倍以上。 DNA 断裂在一到两次分裂中产生，随后细胞适应基因组中的 RNase H2 和核糖核苷酸，并以正常水平的基因组不稳定性生长。 RNase H2 在基因组嵌入的核糖核苷酸上的切割诱导了大规模的全基因组不稳定性和杂合性丢失 (LOH)。
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. Massive pangenome instability and loss of heterozygosity (LOH) induced by RNase H2 cleavage at genomic-embedded ribonucleotides.
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影响因子：
16.6
作者：
Garbacz MA;Lujan SA;Burkholder AB;Cox PB;Wu Q;Zhou ZX;Haber JE;Kunkel TA
通讯作者：
Kunkel TA
影响因子：
14.9
作者：
Chon H;Sparks JL;Rychlik M;Nowotny M;Burgers PM;Crouch RJ;Cerritelli SM
通讯作者：
Cerritelli SM
影响因子：
11.4
作者：
Huang, Shar-yin N.;Williams, Jessica S.;Pommier, Yves
通讯作者：
Pommier, Yves
DOI：
10.1007/978-1-4939-2562-9_3
发表时间：
2015-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Koh, Kyung Duk;Chiu, Hsiang-Chih;Storici, Francesca
通讯作者：
Storici, Francesca
影响因子：
64.5
作者：
ENGELS, WR;PRESTON, CR
通讯作者：
PRESTON, CR