Trujillo Kelly M, Roh Dong Hyun, Chen Ling, Van Komen Stephen, Tomkinson Alan, Sung Patrick
University of Texas Health Science Center, Department of Molecular Medicine, Institute of Biotechnology, San Antonio, Texas 78245, USA.
J Biol Chem. 2003 Dec 5;278(49):48957-64. doi: 10.1074/jbc.M309877200. Epub 2003 Sep 30.
Saccharomyces cerevisiae Rad50, Mre11, and Xrs2 proteins are involved in homologous recombination, non-homologous end-joining, DNA damage checkpoint signaling, and telomere maintenance. These proteins form a stable complex that has nuclease, DNA binding, and DNA end recognition activities. Of the components of the Rad50.Mre11.Xrs2 complex, Xrs2 is the least characterized. The available evidence is consistent with the idea that Xrs2 recruits other protein factors in reactions that pertain to the biological functions of the Rad50.Mre11.Xrs2 complex. Here we present biochemical evidence that Xrs2 has an associated DNA-binding activity that is specific for DNA structures. We also define the contributions of Xrs2 to the activities of the Rad50.Mre11.Xrs2 complex. Importantly, we demonstrate that Xrs2 is critical for targeting of Rad50 and Mre11 to DNA ends. Thus, Xrs2 likely plays a direct role in the engagement of DNA substrates by the Rad50. Mre11.Xrs2 complex in various biological processes.
酿酒酵母的Rad50、Mre11和Xrs2蛋白参与同源重组、非同源末端连接、DNA损伤检查点信号传导以及端粒维持。这些蛋白形成一个稳定的复合物，具有核酸酶、DNA结合和DNA末端识别活性。在Rad50.Mre11.Xrs2复合物的组分中，Xrs2的特征了解最少。现有证据与以下观点一致：在与Rad50.Mre11.Xrs2复合物生物学功能相关的反应中，Xrs2招募其他蛋白质因子。在此，我们提供生化证据表明Xrs2具有与特定DNA结构相关的DNA结合活性。我们还确定了Xrs2对Rad50.Mre11.Xrs2复合物活性的贡献。重要的是，我们证明Xrs2对于将Rad50和Mre11靶向DNA末端至关重要。因此，Xrs2可能在Rad50.Mre11.Xrs2复合物于各种生物学过程中结合DNA底物方面发挥直接作用。
