Dual daughter strand incision is processive and increases the efficiency of DNA mismatch repair.
Dual daughter strand incision is processive and increases the efficiency of DNA mismatch repair.
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DOI：
10.1093/nar/gkw411
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发表时间：
2016-08-19
影响因子：
14.9
通讯作者：
Lebbink JH
中科院分区：
文献类型：
--
作者：
Hermans N;Laffeber C;Cristovão M;Artola-Borán M;Mardenborough Y;Ikpa P;Jaddoe A;Winterwerp HH;Wyman C;Jiricny J;Kanaar R;Friedhoff P;Lebbink JH
DNA错配修复(MMR)是一个进化保守的过程，负责修复复制错误。在大肠杆菌中，MMR由MutS和MutL启动，MutS和MutL激活MUTH来切割瞬时半甲基化的GATC位点。MMR效率取决于这些GATC站点的分布。为了了解哪些分子事件决定了修复效率，我们定量地研究了链切割对解旋和切除活性的影响。错配和GATC位点之间的距离对链切割率没有影响，并且位点数量的增加仅在很小程度上促进了切割。两个GATC位点被同一激活的MMR复合体以连续的方式切割，MutS，MutL和Muth的闭合形式发挥不同的作用。在错配两侧有两个刻痕的衬底上，与在错配的同一侧包含一个刻痕或两个刻痕的衬底相比，解卷和链切除更有效。通过人MutLα内切酶引入多个缺口也有助于提高修复效率。我们的数据支持原核和真核MMR的一般模型，在该模型中，尽管机制不同，错配激活的复合体通过产生多个子链缺口来促进有效的修复。
DNA mismatch repair (MMR) is an evolutionarily-conserved process responsible for the repair of replication errors. In Escherichia coli, MMR is initiated by MutS and MutL, which activate MutH to incise transiently-hemimethylated GATC sites. MMR efficiency depends on the distribution of these GATC sites. To understand which molecular events determine repair efficiency, we quantitatively studied the effect of strand incision on unwinding and excision activity. The distance between mismatch and GATC site did not influence the strand incision rate, and an increase in the number of sites enhanced incision only to a minor extent. Two GATC sites were incised by the same activated MMR complex in a processive manner, with MutS, the closed form of MutL and MutH displaying different roles. Unwinding and strand excision were more efficient on a substrate with two nicks flanking the mismatch, as compared to substrates containing a single nick or two nicks on the same side of the mismatch. Introduction of multiple nicks by the human MutLα endonuclease also contributed to increased repair efficiency. Our data support a general model of prokaryotic and eukaryotic MMR in which, despite mechanistic differences, mismatch-activated complexes facilitate efficient repair by creating multiple daughter strand nicks.
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影响因子：
16
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
通讯作者：
Jiricny, Josef
影响因子：
14.9
作者：
Elez M;Radman M;Matic I
通讯作者：
Matic I
影响因子：
4.8
作者：
Genschel, J;Bazemore, LR;Modrich, P
通讯作者：
Modrich, P
影响因子：
14.9
作者：
Drotschmann, K;Aronshtam, A;Marinus, MG
通讯作者：
Marinus, MG
影响因子：
64.5
作者：
Ban, C;Junop, M;Yang, W
通讯作者：
Yang, W