Incision of damaged DNA in the presence of an impaired Smc5/6 complex imperils genome stability.
Incision of damaged DNA in the presence of an impaired Smc5/6 complex imperils genome stability.
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DOI：
10.1093/nar/gkw720
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发表时间：
2016-12-01
影响因子：
14.9
通讯作者：
Feng W
中科院分区：
文献类型：
--
作者：
Peng J;Feng W
Smc5/6复合体在DNA损伤或复制应激过程中参与同源重组介导的DNA修复。在这里，我们分析了一个亚形发芽酵母突变体smc6-P4的全基因组复制动力学。在smc6突变体中的总体复制动态与野生型细胞中的类似。然而，我们在突变体中捕获了S早期样本的复制图谱中的差异，从而提出了这样的假设，即突变体在复制过程中加入了核苷酸和/或积累了单链DNA缺口。我们测试了抑制核苷酸切除修复途径是否会加剧smc6突变体对DNA复制压力的反应。与我们的预期相反，核苷酸切除修复以及几乎所有其他DNA修复途径的损伤，缓解了smc6突变体对诱导复制应激的超敏反应。我们认为，在没有功能性Smc5/6复合体的情况下，核苷酸切开比损伤本身具有更多的灾难性后果。我们的研究为Smc5/6复合体在DNA复制中的作用提供了新的视角。
The Smc5/6 complex is implicated in homologous recombination-mediated DNA repair during DNA damage or replication stress. Here, we analysed genome-wide replication dynamics in a hypomorphic budding yeast mutant, smc6-P4. The overall replication dynamics in the smc6 mutant is similar to that in the wild-type cells. However, we captured a difference in the replication profile of an early S phase sample in the mutant, prompting the hypothesis that the mutant incorporates ribonucleotides and/or accumulates single-stranded DNA gaps during replication. We tested if inhibiting the ribonucleotide excision repair pathway would exacerbate the smc6 mutant in response to DNA replication stress. Contrary to our expectation, impairment of ribonucleotide excision repair, as well as virtually all other DNA repair pathways, alleviated smc6 mutant's hypersensitivity to induced replication stress. We propose that nucleotide incision in the absence of a functional Smc5/6 complex has more disastrous outcomes than the damage per se. Our study provides novel perspectives for the role of the Smc5/6 complex during DNA replication.
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影响因子：
21.3
作者：
Feng, Wenyi;Collingwood, David;Boeck, Max E;Fox, Lindsay A;Alvino, Gina M;Fangman, Walton L;Raghuraman, Mosur K;Brewer, Bonita J
通讯作者：
Brewer, Bonita J
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：
Chon H;Sparks JL;Rychlik M;Nowotny M;Burgers PM;Crouch RJ;Cerritelli SM
通讯作者：
Cerritelli SM
DOI：
10.1126/science.1219379
发表时间：
2012-09-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cloud V;Chan YL;Grubb J;Budke B;Bishop DK
通讯作者：
Bishop DK
影响因子：
16
作者：
Cho, RJ;Campbell, MJ;Davis, RW
通讯作者：
Davis, RW