Regulation of Metnase's TIR binding activity by its binding partner, Pso4.
Regulation of Metnase's TIR binding activity by its binding partner, Pso4.
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DOI：
10.1016/j.abb.2010.04.011
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发表时间：
2010-06-15
影响因子：
3.9
通讯作者：
Lee, Suk-Hee
中科院分区：
文献类型：
--
作者：
Beck, Brian D.;Lee, Sung S.;Hromas, Robert;Lee, Suk-Hee
Metnase（也称为SETMAR）是人类中的SET和转座酶融合蛋白，在双链断裂（DSB）修复中起积极作用。SET结构域具有组蛋白赖氨酸甲基转移酶活性，而转座酶结构域负责5′-末端反向重复序列（TIR）特异性结合、DNA成环和DNA切割活性。我们最近证明了Pso 4的人类同源物（hPso 4）是介导Metnase与非TIR DNA如DNA损伤位点结合的Metnase结合伴侣。在这里，我们表明，Metnase功能作为二聚体在其TIR结合。虽然Metnase和hPso 4都可以独立地与TIR DNA相互作用，但Metnase的DNA结合活性对于Metnase-hPso 4-DNA复合物的形成并不是必需的。进一步的化学计量分析表明，当Metnase-hPso 4形成稳定的复合物时，只有一种蛋白质参与与dsDNA的相互作用。Metnase-hPso 4复合物与TIR DNA的相互作用被TIR和非TIR DNA竞争性抑制，表明hPso 4仅负责与Metnase-hPso 4-DNA复合物中的DNA结合。总之，我们的研究表明，hPso 4，一旦它与Metnase形成复合物，负调节Metnase的TIR结合活性，这可能是必要的Metnase定位在非TIR位点，如DSBs。
Metnase (also known as SETMAR) is a SET and transposase fusion protein in humans and plays a positive role in double-strand break (DSB) repair. While the SET domain possesses histone lysine methyltransferase activity, the transposase domain is responsible for 5′-terminal inverted repeat (TIR)-specific binding, DNA looping, and DNA cleavage activities. We recently demonstrated that human homolog of Pso4 (hPso4) is a Metnase binding partner that mediates Metnase binding to non-TIR DNA such as DNA damage sites. Here we show that Metnase functions as a dimer in its TIR binding. While both Metnase and hPso4 can independently interact with TIR DNA, Metnase’s DNA binding activity is not required for formation of the Metnase-hPso4-DNA complex. A further stoichiometric analysis indicated that only one protein is involved in interaction with dsDNA when Metnase-hPso4 forms a stable complex. Interaction of the Metnase-hPso4 complex with TIR DNA was competitively inhibited by both TIR and non-TIR DNA, suggesting that hPso4 is solely responsible for binding to DNA in the Metnase-hPso4-DNA complex. Together, our study suggests that hPso4, once it forms a complex with Metnase, negatively regulates Metnase’s TIR binding activity, which is perhaps necessary for Metnase localization at non-TIR sites such as DSBs.
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DOI：
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发表时间：
2003-11-01
影响因子：
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作者：
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