Frequency and patterns of ribonucleotide incorporation around autonomously replicating sequences in yeast reveal the division of labor of replicative DNA polymerases.
Frequency and patterns of ribonucleotide incorporation around autonomously replicating sequences in yeast reveal the division of labor of replicative DNA polymerases.
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DOI：
10.1093/nar/gkab801
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发表时间：
2021-10-11
影响因子：
14.9
通讯作者：
Storici F
中科院分区：
文献类型：
--
作者：
Xu P;Storici F
三磷酸核糖核苷（rNTP）通过DNA聚合酶掺入DNA中是一种常见的现象，导致DNA结构改变和基因组不稳定。然而，目前还不清楚rNTP掺入DNA是否遵循任何特定的序列模式。我们分析了嵌入DNA中的核糖核苷单磷酸（rNMP）的多个数据集，这些数据集由三种rNMP测序技术生成。这些rNMP文库从表达野生型或突变型复制型DNA聚合酶和核糖核酸酶H2基因的酿酒酵母细胞获得。我们进行了计算分析的rNMP网站周围的早期和晚期发射自主复制序列（ARS）的酵母基因组，领先和落后的DNA合成开始双向。我们发现，在野生型DNA聚合酶酵母细胞的前导链上的rNTP掺入的偏好。rNTP掺入的前导/滞后链比率在来自ARS的前1，000个核苷酸内急剧变化，突出了在早期前导链合成期间的Pol δ - Pol δ传递。此外，rNTP掺入的模式不仅在突变体中而且在野生型聚合酶细胞中的前导链和滞后链之间是明显不同的。Pol δ和Pol γ的这种特异性特征提供了一种新的方法来跟踪这些聚合酶的劳动。
Ribonucleoside triphosphate (rNTP) incorporation in DNA by DNA polymerases is a frequent phenomenon that results in DNA structural change and genome instability. However, it is unclear whether the rNTP incorporation into DNA follows any specific sequence patterns. We analyzed multiple datasets of ribonucleoside monophosphates (rNMPs) embedded in DNA, generated from three rNMP-sequencing techniques. These rNMP libraries were obtained from Saccharomyces cerevisiae cells expressing wild-type or mutant replicative DNA polymerase and ribonuclease H2 genes. We performed computational analyses of rNMP sites around early and late-firing autonomously replicating sequences (ARSs) of the yeast genome, where leading and lagging DNA synthesis starts bidirectionally. We found the preference of rNTP incorporation on the leading strand in wild-type DNA polymerase yeast cells. The leading/lagging-strand ratio of rNTP incorporation changes dramatically within the first 1,000 nucleotides from ARSs, highlighting the Pol δ - Pol ϵ handoff during early leading-strand synthesis. Furthermore, the pattern of rNTP incorporation is markedly distinct between the leading and lagging strands not only in mutant but also in wild-type polymerase cells. Such specific signatures of Pol δ and Pol ϵ provide a new approach to track the labor of these polymerases.
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DOI：
10.1111/gtc.12871
发表时间：
2021-08
期刊：
Genes to cells : devoted to molecular & cellular mechanisms
影响因子：
--
作者：
Iida T;Iida N;Sese J;Kobayashi T
通讯作者：
Kobayashi T
从DNA中酶促去除核糖核苷酸对于哺乳动物的基因组完整性和发育至关重要。
影响因子：
64.5
作者：
Reijns MA;Rabe B;Rigby RE;Mill P;Astell KR;Lettice LA;Boyle S;Leitch A;Keighren M;Kilanowski F;Devenney PS;Sexton D;Grimes G;Holt IJ;Hill RE;Taylor MS;Lawson KA;Dorin JR;Jackson AP
通讯作者：
Jackson AP
影响因子：
14.9
作者：
Gombolay AL;Vannberg FO;Storici F
通讯作者：
Storici F
影响因子：
16
作者：
Sparks, Justin L.;Chon, Hyongi;Cerritelli, Susana M.;Kunkel, Thomas A.;Johansson, Erik;Crouch, Robert J.;Burgers, Peter M.
通讯作者：
Burgers, Peter M.
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