Evidence that DNA polymerase δ contributes to initiating leading strand DNA replication in Saccharomyces cerevisiae.
Evidence that DNA polymerase δ contributes to initiating leading strand DNA replication in Saccharomyces cerevisiae.
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DOI：
10.1038/s41467-018-03270-4
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发表时间：
2018-02-27
影响因子：
16.6
通讯作者：
Kunkel TA
中科院分区：
文献类型：
--
作者：
Garbacz MA;Lujan SA;Burkholder AB;Cox PB;Wu Q;Zhou ZX;Haber JE;Kunkel TA
为了研究体内核DNA复制酶学，我们研究了含有pol 2 -16突变的酿酒酵母菌株，该突变使DNA聚合酶ε（Pol ε）的催化活性失活。尽管pol 2 -16突变体存活，但它们呈现非常小的孢子集落、增加的倍增时间、比正常细胞大、异常的细胞核和快速获得抑制突变。这些表型揭示了与仅缺乏Pol ε校正（pol 2 -4）的菌株不同的严重生长缺陷，这与Pol ε是用于无应激DNA复制的主要前导链聚合酶的观点一致。当Pol ε不存在时，核糖核苷酸以与Pol δ的前导链复制一致的模式掺入pol 2 -16基因组中。更重要的是，复制起点的核糖核苷酸分布表明，在编码所有三种复制酶的菌株中，Pol δ有助于起始前导链复制。我们描述了两种可能的模型。DNA聚合酶δ和ε（Pol δ和ε）被认为分别负责滞后链和前导链的合成。在这里，作者提出了证据，证明Pol δ通过在复制起点合成两条链的DNA，有助于芽殖酵母中引导链复制的启动。
To investigate nuclear DNA replication enzymology in vivo, we have studied Saccharomyces cerevisiae strains containing a pol2-16 mutation that inactivates the catalytic activities of DNA polymerase ε (Pol ε). Although pol2-16 mutants survive, they present very tiny spore colonies, increased doubling time, larger than normal cells, aberrant nuclei, and rapid acquisition of suppressor mutations. These phenotypes reveal a severe growth defect that is distinct from that of strains that lack only Pol ε proofreading (pol2-4), consistent with the idea that Pol ε is the major leading-strand polymerase used for unstressed DNA replication. Ribonucleotides are incorporated into the pol2-16 genome in patterns consistent with leading-strand replication by Pol δ when Pol ε is absent. More importantly, ribonucleotide distributions at replication origins suggest that in strains encoding all three replicases, Pol δ contributes to initiation of leading-strand replication. We describe two possible models. DNA polymerases δ and ε (Pols δ and ε) are thought to be responsible for lagging and leading strand synthesis, respectively. Here the authors present evidence that Pol δ contributes to the initiation of leading strand replication in budding yeast by synthesizing DNA of both strands at replication origins.
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影响因子：
3.3
作者：
Bell SP;Labib K
通讯作者：
Labib K
影响因子：
64.5
作者：
Haradhvala NJ;Polak P;Stojanov P;Covington KR;Shinbrot E;Hess JM;Rheinbay E;Kim J;Maruvka YE;Braunstein LZ;Kamburov A;Hanawalt PC;Wheeler DA;Koren A;Lawrence MS;Getz G
通讯作者：
Getz G
DOI：
10.1073/pnas.1418334111
发表时间：
2014-10-28
影响因子：
11.1
作者：
Langston, Lance D.;Zhang, Dan;O'Donnell, Mike E.
通讯作者：
O'Donnell, Mike E.
影响因子：
10.5
作者：
Lydeard, John R.;Lipkin-Moore, Zachary;Haber, James E.
通讯作者：
Haber, James E.
真核铅和滞后链DNA聚合酶通过单独的机制加载到引物上，但在PCNA存在下具有可比的加工性。
影响因子：
14.9
作者：
Chilkova O;Stenlund P;Isoz I;Stith CM;Grabowski P;Lundström EB;Burgers PM;Johansson E
通讯作者：
Johansson E