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首页> 外文期刊>Molecular and Cellular Biology >HOXD13 Binds DNA Replication Origins To Promote Origin Licensing and Is Inhibited by Geminin
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HOXD13 Binds DNA Replication Origins To Promote Origin Licensing and Is Inhibited by Geminin

机译：HOXD13绑定DNA复制起点，以促进起点许可并被Geminin抑制

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摘要

HOX DNA-binding proteins control patterning during development by regulating processes such as cell aggregation and proliferation. Recently, a possible involvement of HOX proteins in replication origin activity was suggested by results showing that a number of HOX proteins interact with the DNA replication licensing regulator geminin and bind a characterized human origin of replication. The functional significance of these observations, however, remained unclear. We show that HOXD13, HOXD11, and HOXA13 bind in vivo all characterized human replication origins tested. We furthermore show that HOXD13 interacts with the CDC6 loading factor, promotes pre-replication complex (pre-RC) proteins assembly at origins, and stimulates DNA synthesis in an in vivo replication assay. HOXD13 expression in cultured cells accelerates DNA synthesis initiation in correlation with the earlier pre-RC recruitment onto origins during G1 phase. Geminin, which interacts with HOXD13 as well, blocks HOXD13-mediated assembly of pre-RC proteins and inhibits HOXD13-induced DNA replication. Our results uncover a function for Hox proteins in the regulation of replication origin activity and reveal an unforeseen role for the inhibition of HOX protein activity by geminin in the context of replication origin licensing.
机译：HOX DNA结合蛋白通过调节细胞聚集和增殖等过程来控制发育过程中的模式。最近，结果表明，许多HOX蛋白与DNA复制许可调节剂geminin相互作用并结合特征性的人类复制起点，表明HOX蛋白可能参与复制起点活性。但是，这些观察的功能意义仍然不清楚。我们显示HOXD13，HOXD11和HOXA13体内结合所有测试的特征性人类复制起源。我们还显示，HOXD13与CDC6加载因子相互作用，在起源处促进复制前复合物（pre-RC）蛋白质装配，并在体内复制试验中刺激DNA合成。培养细胞中HOXD13的表达与G 1 阶段中较早的RC早期募集相关，从而加速了DNA合成的启动。 Geminin也与HOXD13相互作用，可阻断HOXD13介导的pre-RC蛋白组装并抑制HOXD13诱导的DNA复制。我们的研究结果揭示了Hox蛋白在复制起点活性调控中的功能，并揭示了在复制起点许可的情况下geminin抑制HOX蛋白活性的不可预测的作用。

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