Genetic and functional interactions between Mus81-Mms4 and Rad27.
Genetic and functional interactions between Mus81-Mms4 and Rad27.
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DOI：
10.1093/nar/gkq651
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发表时间：
2010-11
影响因子：
14.9
通讯作者：
Seo YS
中科院分区：
文献类型：
--
作者：
Kang MJ;Lee CH;Kang YH;Cho IT;Nguyen TA;Seo YS
这两种核酸内切酶，Rad 27（酵母Fen 1）和DNA 2，共同参与冈崎片段在酵母中的加工。Mus 81-Mms 4是一种结构特异性核酸内切酶，可以解析停滞的复制叉以及有毒的重组中间体。在这项研究中，我们表明，Mus 81-Mms 4可以抑制dna 2突变缺陷凭借其功能和物理相互作用与Rad 27。Mus 81-Mms 4显著刺激了Rad 27的活性，说明其能够恢复由DNA 2突变引起的生长缺陷。有趣的是，Rad 27刺激了Mus 81-Mms 4催化的各种底物（包括退化的复制叉底物）裂解的速率。Rad 27刺激Mus 81-Mms 4的能力不依赖于Rad 27的催化活性，但需要Rad 27的C-末端64个氨基酸片段。这表明刺激是由两种蛋白质之间的特异性蛋白质-蛋白质相互作用介导的。我们的体外数据表明，Mus 81-Mms 4和Rad 27在DNA复制过程中共同作用，并解决了可能阻碍正常DNA复制的各种结构。rad 27 mus 81或rad 27 mms 4双突变体协同致死的事实进一步加强了这一结论。我们讨论了Rad 27，DNA 2和Mus 81-Mms 4之间的相互作用在DNA复制的背景下的意义。
The two endonucleases, Rad27 (yeast Fen1) and Dna2, jointly participate in the processing of Okazaki fragments in yeasts. Mus81–Mms4 is a structure-specific endonuclease that can resolve stalled replication forks as well as toxic recombination intermediates. In this study, we show that Mus81–Mms4 can suppress dna2 mutational defects by virtue of its functional and physical interaction with Rad27. Mus81–Mms4 stimulated Rad27 activity significantly, accounting for its ability to restore the growth defects caused by the dna2 mutation. Interestingly, Rad27 stimulated the rate of Mus81–Mms4 catalyzed cleavage of various substrates, including regressed replication fork substrates. The ability of Rad27 to stimulate Mus81–Mms4 did not depend on the catalytic activity of Rad27, but required the C-terminal 64 amino acid fragment of Rad27. This indicates that the stimulation was mediated by a specific protein–protein interaction between the two proteins. Our in vitro data indicate that Mus81–Mms4 and Rad27 act together during DNA replication and resolve various structures that can impede normal DNA replication. This conclusion was further strengthened by the fact that rad27 mus81 or rad27 mms4 double mutants were synergistically lethal. We discuss the significance of the interactions between Rad27, Dna2 and Mus81–Mms4 in context of DNA replication.
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影响因子：
16
作者：
Chen, XB;Melchionna, R;McGowan, CH
通讯作者：
McGowan, CH
影响因子：
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