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首页> 外文期刊>Journal of Molecular Biology >The characterization of Saccharomyces cerevisiae Mre11/Rad50/Xrs2 complex reveals that rad50 negatively regulates Mre11 endonucleolytic but not the exonucleolytic activity
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The characterization of Saccharomyces cerevisiae Mre11/Rad50/Xrs2 complex reveals that rad50 negatively regulates Mre11 endonucleolytic but not the exonucleolytic activity

机译：酿酒酵母Mre11 / Rad50 / Xrs2复合体的表征表明，rad50负调控Mre11内切核酸酶，但不是外切核酸酶活性。

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摘要

The evolutionarily conserved heterotrimeric Mre11/Rad50/Xrs2 (Nbs1) (MRX/N) complex plays a central role in an array of cellular responses involving DNA damage, telomere length homeostasis, cell-cycle checkpoint control and meiotic recombination. The underlying biochemical functions of MRX/N complex, or each of its individual subunits, at telomeres and the importance of complex formation are poorly understood. Here, we show that the Saccharomyces cerevisiae MRX complex, or its subunits, display an overwhelming preference for G-quadruplex DNA than for telomeric single-stranded or double-stranded DNA implicating the possible existence of this DNA structure in vivo. Although these alternative DNA substrates failed to affect Rad50 ATPase activity, kinetic analyses revealed that interaction of Rad50 with Xrs2 and/or Mre11 led to a twofold increase in the rates of ATP hydrolysis. Significantly, we show that Mre11 displays sequence-specific double-stranded DNA endonuclease activity, and Rad50, but not Xrs2, abrogated endonucleolytic but not the exonucleolytic activity. This repression was alleviated upon ATP hydrolysis by Rad50, suggesting that complex formation between Rad50 and Mre11 might be important for blocking the inappropriate cleavage of genomic DNA. Mre11 alone, or in the presence of ATP, MRX, MR or MX sub-complexes cleaved at the 5' end of an array of G residues in single-stranded DNA, at G quartets in G4 DNA, and at the center of TGTG repeats in duplex DNA. We propose that negative regulation of Mre11 endonuclease activity by Rad50 might be important for native as well as de novo telomere length homeostasis. (c) 2007 Elsevier Ltd. All rights reserved.
机译：进化保守的异三聚体Mre11 / Rad50 / Xrs2（Nbs1）（MRX / N）复合物在涉及DNA损伤，端粒长度稳态，细胞周期检查点控制和减数分裂重组的一系列细胞反应中起着核心作用。人们对MRX / N复合物或其每个亚基在端粒的潜在生化功能以及复合物形成的重要性了解得很少。在这里，我们显示酿酒酵母MRX复杂或其亚基显示出比G端四链体DNA压倒性的优势，而不是端粒单链或双链DNA暗示了这种DNA结构在体内的存在。尽管这些替代的DNA底物不能影响Rad50 ATPase的活性，但动力学分析表明Rad50与Xrs2和/或Mre11的相互作用导致ATP水解速率增加了两倍。重要的是，我们显示Mre11显示序列特定的双链DNA核酸内切酶活性，Rad50（而非Xrs2）消除了内切核酸酶活性，但废除了核酸外切酶活性。 Rad50水解ATP后，这种抑制作用得以缓解，这表明Rad50和Mre11之间的复合物形成可能对阻止基因组DNA的不适当切割很重要。单独的Mre11或存在于ATP，MRX，MR或MX亚复合物的单链DNA的G残基阵列的5'末端，G4 DNA的G四重体和TGTG重复序列的中央在双链DNA中。我们建议，Rad50对Mre11核酸内切酶活性的负调节对于天然的和从头端的端粒长度稳态可能很重要。 （c）2007 Elsevier Ltd.保留所有权利。

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