Pol2 is the leading-strand DNA polymerase in budding yeast. Here we describe an antagonism between its conserved POPS (Pol2 family-specific catalytic core peripheral subdomain) and exonuclease domain and the importance of this antagonism in genome replication. We show that multiple defects caused by POPS mutations, including impaired growth and DNA synthesis, genome instability, and reliance on other genome maintenance factors, were rescued by exonuclease inactivation. Single-molecule data revealed that the rescue stemmed from allowing sister replication forks to progress at equal rates. Our data suggest that balanced activity of Pol2's POPS and exonuclease domains is vital for genome replication and stability.

中文翻译：

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前导链 DNA 聚合酶特异性结构域及其核酸外切酶结构域的平衡作用促进全基因组姐妹复制叉对称性

Pol2 是芽殖酵母中的主导链 DNA 聚合酶。在这里，我们描述了其保守的 POPS（Pol2 家族特异性催化核心外围子结构域）和核酸外切酶结构域之间的拮抗作用，以及这种拮抗作用在基因组复制中的重要性。我们发现，POPS 突变引起的多种缺陷，包括生长和 DNA 合成受​​损、基因组不稳定以及对其他基因组维护因素的依赖，都可以通过核酸外切酶失活来挽救。单分子数据显示，拯救源于允许姐妹复制叉以相同的速率进行。我们的数据表明，Pol2 的 POPS 和核酸外切酶结构域的平衡活性对于基因组复制和稳定性至关重要。