The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage.
The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage.
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DOI：
10.1038/ncomms7746
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发表时间：
2015-04-16
影响因子：
16.6
通讯作者：
Aladjem, Mirit I.
中科院分区：
文献类型：
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作者：
Fu, Haiqing;Martin, Melvenia M.;Regairaz, Marie;Huang, Liang;You, Yang;Lin, Chi-Mei;Ryan, Michael;Kim, RyangGuk;Shimura, Tsutomu;Pommier, Yves;Aladjem, Mirit I.
Mus81核酸内切酶分解重组中间体并介导细胞对外源复制应激的应答。在这里，我们表明，Mus81也调节DNA复制的速度在正常生长过程中，通过促进复制叉进展，同时降低复制起始事件的频率。在缺乏Mus81核酸内切酶活性的情况下，DNA合成减慢，复制起始事件更频繁。此外，Mus81缺陷型细胞不能从暴露于低剂量复制抑制剂中恢复，并且细胞活力依赖于XPF内切核酸酶。尽管复制起始频率增加，但缺乏Mus81的细胞与表达Mus81的细胞使用相同的复制起点库。因此，Mus81缺陷细胞中的减速DNA复制不是从正常生长期间不使用的隐蔽或潜伏的起点开始的。这些结果表明，Mus81在决定DNA复制速率方面起着关键作用，而不激活一组新的复制起点。
The Mus81 endonuclease resolves recombination intermediates and mediates cellular responses to exogenous replicative stress. Here, we show that Mus81 also regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication initiation events. In the absence of Mus81 endonuclease activity, DNA synthesis is slowed and replication initiation events are more frequent. In addition, Mus81 deficient cells fail to recover from exposure to low doses of replication inhibitors and cell viability is dependent on the XPF endonuclease. Despite an increase in replication initiation frequency, cells lacking Mus81 use the same pool of replication origins as Mus81-expressing cells. Therefore, decelerated DNA replication in Mus81 deficient cells does not initiate from cryptic or latent origins not used during normal growth. These results indicate that Mus81 plays a key role in determining the rate of DNA replication without activating a novel group of replication origins.
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影响因子：
64.5
作者：
Casper, AM;Nghiem, P;Glover, TW
通讯作者：
Glover, TW
影响因子：
9.8
作者：
Demczuk A;Gauthier MG;Veras I;Kosiyatrakul S;Schildkraut CL;Busslinger M;Bechhoefer J;Norio P
通讯作者：
Norio P
影响因子：
16
作者：
Chen, XB;Melchionna, R;McGowan, CH
通讯作者：
McGowan, CH
影响因子：
10.5
作者：
Ge, Xin Quan;Jackson, Dean A;Blow, J Julian
通讯作者：
Blow, J Julian
DOI：
10.1038/nrm1663
发表时间：
2005-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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