The ability for DNA polymerases (Pols) to overcome a variety of obstacles in its path to maintain genomic stability during replication is a complex endeavor. It requires the coordination of multiple Pols with differing specificities through molecular control and access to the replisome. Although a number of contacts directly between Pols and accessory proteins have been identified, forming the basis of a variety of holoenzyme complexes, the dynamics of Pol active site substitutions remain uncharacterized. Substitutions can occur externally by recruiting new Pols to replisome complexes through an “exchange” of enzyme binding or internally through a “switch” in the engagement of DNA from preformed associated enzymes contained within supraholoenzyme complexes. Models for how high fidelity (HiFi) replication Pols can be substituted by translesion synthesis (TLS) Pols at sites of damage during active replication will be discussed. These substitution mechanisms may be as diverse as the number of Pol families and types of damage; however, common themes can be recognized across species. Overall, Pol substitutions will be controlled by explicit protein contacts, complex multiequilibrium processes, and specific kinetic activities. Insight into how these dynamic processes take place and are regulated will be of utmost importance for our greater understanding of the specifics of TLS as well as providing for future novel chemotherapeutic and antimicrobial strategies.

中文翻译：

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DNA聚合酶的协调和取代对基因组障碍的反应。

DNA聚合酶（Pol）克服其在复制过程中维持基因组稳定性的途径中的各种障碍的能力是一项复杂的工作。它需要通过分子控制和接近复制体来协调具有不同特异性的多个Pol。尽管已经确定了Pols和辅助蛋白之间的许多直接接触，形成了多种全酶复合物的基础，但Pol活性位点取代的动力学仍未表征。替代可以通过在外部通过结合酶的“交换”募集新的Pols至复制体复合体来实现，也可以在内部通过“开关”从DNA参与超核酶复合体中预先形成的相关酶的参与中“转换”而发生。将讨论在主动复制过程中损坏位置的高保真（HiFi）复制Pols可以被跨病变合成（TLS）Pols取代的模型。这些替代机制可能与Pol家族的数量和损害的类型一样多样。但是，共同的主题可以跨物种识别。总体而言，Pol取代将受明确的蛋白质接触，复杂的多平衡过程和特定的动力学活性控制。深入了解这些动态过程是如何发生和受到监管的，对于我们对TLS细节的深入了解以及为将来的新型化学疗法和抗菌策略提供参考至关重要。这些替代机制可能与Pol家族的数量和损害的类型一样多样。但是，共同的主题可以跨物种识别。总体而言，Pol取代将受明确的蛋白质接触，复杂的多平衡过程和特定的动力学活性控制。深入了解这些动态过程是如何发生和受到监管的，对于我们对TLS细节的深入了解以及为将来的新型化学疗法和抗菌策略提供参考至关重要。这些替代机制可能与Pol家族的数量和损害的类型一样多样。但是，共同的主题可以跨物种识别。总体而言，Pol取代将受明确的蛋白质接触，复杂的多平衡过程和特定的动力学活性控制。深入了解这些动态过程是如何发生和受到监管的，对于我们对TLS细节的深入了解以及为将来的新型化学疗法和抗菌策略提供参考至关重要。