Sumoylation is emerging as a posttranslation modification important for regulating chromosome duplication and stability. The origin recognition complex (ORC) that directs DNA replication initiation by loading the MCM replicative helicase onto origins is sumoylated in both yeast and human cells. However, the biological consequences of ORC sumoylation are unclear. Here we report the effects of hypersumoylation and hyposumoylation of yeast ORC on ORC activity and origin function using multiple approaches. ORC hypersumoylation preferentially reduced the function of a subset of early origins, while Orc2 hyposumoylation had an opposing effect. Mechanistically, ORC hypersumoylation reduced MCM loading in vitro and diminished MCM chromatin association in vivo. Either hypersumoylation or hyposumoylation of ORC resulted in genome instability and the dependence of yeast on other genome maintenance factors, providing evidence that appropriate ORC sumoylation levels are important for cell fitness. Thus, yeast ORC sumoylation status must be properly controlled to achieve optimal origin function across the genome and genome stability.

中文翻译：

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酵母 ORC sumoylation 状态微调原产地许可


Sumoylation 是一种新兴的翻译后修饰，对于调节染色体复制和稳定性非常重要。通过将 MCM 复制解旋酶加载到起点上来指导 DNA 复制起始的起点识别复合物 (ORC) 在酵母和人类细胞中均被苏酰化。然而，ORC 苏酰化的生物学后果尚不清楚。在这里，我们使用多种方法报告了酵母 ORC 的高素酰化和低素酰化对 ORC 活性和起源功能的影响。 ORC 超素酰化优先降低早期起源子集的功能，而 Orc2 低素酰化则具有相反的作用。从机制上讲，ORC 超苏酰化在体外减少了 MCM 负载，并在体内减少了 MCM 染色质关联。 ORC 的高素酰化或低素酰化都会导致基因组不稳定以及酵母对其他基因组维持因子的依赖性，这提供了适当的 ORC 素酰化水平对于细胞适应性非常重要的证据。因此，必须适当控制酵母 ORC sumoylation 状态，以实现整个基因组的最佳起源功能和基因组稳定性。