Ribonucleotides misincorporated into DNA act as strand-discrimination signals in eukaryotic mismatch repair.
Ribonucleotides misincorporated into DNA act as strand-discrimination signals in eukaryotic mismatch repair.
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DOI：
10.1016/j.molcel.2013.03.019
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发表时间：
2013-05-09
期刊：
影响因子：
16
通讯作者：
Jiricny, Josef
中科院分区：
文献类型：
--
作者：
Ghodgaonkar, Medini Manohar;Lazzaro, Federico;Olivera-Pimentel, Maite;Artola-Boran, Mariela;Cejka, Petr;Reijns, Martin A.;Jackson, Andrew P.;Plevani, Paolo;Muzi-Falconi, Marco;Jiricny, Josef
为了提高复制保真度，错配修复（MMR）必须检测非沃森-克里克碱基对，并将其修复导向新生DNA链。真核生物体外MMR需要预先存在的链不连续来启动；因此，有假设认为，体内MMR始于后链的冈崎片段末端，以及由错配激活的MLH1/PMS2内切酶在前导链上产生的缺口。我们现在表明，在人类细胞提取物中，错配附近的单个核糖核苷酸可以作为MMR的起始位点，并且该系统中的MMR激活依赖于RNase H2。由于s.c reevisiae中RNase H2的缺失导致轻微的MMR缺陷，这反映在突变增加上，体内的MMR也可能在RNase H2产生的切口处启动。因此，我们提出在DNA复制过程中错误结合的核糖核苷酸作为新生DNA链的生理标记。►整合到真核生物DNA中的核糖核苷酸不是错配修复底物►rNMP加工的中间体可以作为错配修复的起始位点►葡萄链球菌中RNase H2缺乏会降低MMR效率►rNMP可以作为新生DNA链的标记物
To improve replication fidelity, mismatch repair (MMR) must detect non-Watson-Crick base pairs and direct their repair to the nascent DNA strand. Eukaryotic MMR in vitro requires pre-existing strand discontinuities for initiation; consequently, it has been postulated that MMR in vivo initiates at Okazaki fragment termini in the lagging strand and at nicks generated in the leading strand by the mismatch-activated MLH1/PMS2 endonuclease. We now show that a single ribonucleotide in the vicinity of a mismatch can act as an initiation site for MMR in human cell extracts and that MMR activation in this system is dependent on RNase H2. As loss of RNase H2 in S.cerevisiae results in a mild MMR defect that is reflected in increased mutagenesis, MMR in vivo might also initiate at RNase H2-generated nicks. We therefore propose that ribonucleotides misincoporated during DNA replication serve as physiological markers of the nascent DNA strand. ► Ribonucleotides incorporated into eukaryotic DNA are not mismatch repair substrates ► Intermediates of rNMP processing can act as initiation sites for mismatch repair ► RNase H2 deficiency in S. cerevisiae decreases MMR efficiency ► rNMPs can act as markers of nascent DNA strands
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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：
9.2
作者：
Cejka, P;Mojas, N;Jiricny, J
通讯作者：
Jiricny, J
影响因子：
4.7
作者：
Andersen, S;Heine, T;Nilsen, H
通讯作者：
Nilsen, H
DOI：
10.1084/jem.20120876
发表时间：
2012-07-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hiller B;Achleitner M;Glage S;Naumann R;Behrendt R;Roers A
通讯作者：
Roers A
影响因子：
5.3
作者：
Russo, MT;Blasi, MF;Bignami, M
通讯作者：
Bignami, M