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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A structural role for ATP in the formation and stability of the human origin recognition complex
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A structural role for ATP in the formation and stability of the human origin recognition complex

机译：ATP在人类起源识别复合体的形成和稳定性中的结构作用

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摘要

The locally restricted recruitment of the multisubunit origin recognition complex (ORC) to eukaryotic chromosomes defines the position of origins of DNA replication. In budding yeast and metazoans the DNA binding activity of ORC is stimulated by ATP and requires an AAA+-type nucleotide binding domain in the largest subunit. Little else is known about the mechanisms behind the ATP requirement for ORC in its initiator function and, specifically, the relevance of nucleotide binding domains present on other subunits. Here we show that ATP is required for specific subunit interactions in the human ORC, with the Orc4 subunit playing a critical role in this dynamic process. ATP is essential for the maintenance of ORC integrity and facilitates complex formation. Thus, besides its previously identified role in DNA binding, ATP serves also as a structural cofactor for human ORC.
机译：多亚基起源识别复合物（ORC）的局部限制募集到真核染色体定义了DNA复制起源的位置。在发芽的酵母和后生动物中，ORC的DNA结合活性受ATP刺激，并且在最大的亚基中需要AAA +型核苷酸结合域。关于ORC的ATP引发剂功能中的ATP需求背后的机制，尤其是其他亚基上存在的核苷酸结合域的相关性，了解甚少。在这里，我们显示了人类ORC中特定亚基相互作用所需的ATP，而Orc4亚基在此动态过程中起关键作用。 ATP对于维持ORC完整性至关重要，并有助于形成复杂分子。因此，除了先前确定的在DNA结合中的作用外，ATP还充当人类ORC的结构辅因子。

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