Certain replication-blocking lesions can escape DNA repair and must be bypassed to prevent fork collapse and cell death. Budding yeast DNA-damage tolerance consists of translesion DNA synthesis (TLS) and template switch. TLS utilizes specialized DNA polymerases to insert nucleotides opposite the damage site, followed by extension, allowing continual replication in the presence of lesions on the template DNA. Meanwhile, Rev1 is additionally required for the subsequent extension step of TLS regardless of the initial insertion polymerase utilized. Here we assess relative contributions of two Y-family TLS polymerases, Rev1 and Polη, in bypassing lesions induced by various types of DNA-damaging agents. Our experimental results collectively indicate that yeast cells preferentially utilize relatively error-free TLS polymerase(s) to bypass given lesions, and that the mutagenic TLS polymerase may serve as a backup. Interestingly, if Polη is unable to serve as a TLS polymerase under certain circumstances, it may be counter-active. The cooperation among TLS polymerases may strike a balance between survival and stress-induced mutagenesis. These observations indicate that specialized Y-family DNA polymerases have evolved to deal with different types of environmental genotoxic stresses.

某些阻止复制的病变可以逃脱DNA修复，必须绕过以防止叉子塌陷和细胞死亡。酵母DNA的芽损伤耐受性包括转病DNA合成（TLS）和模板转换。TLS利用专门的DNA聚合酶插入与损伤部位相对的核苷酸，然后延伸，从而允许在模板DNA上存在损伤的情况下连续复制。同时，无论采用何种初始插入聚合酶，后续的TLS延伸步骤都需要Rev1。在这里，我们评估了两种Y家族TLS聚合酶Rev1和Polη在绕过由各种类型的DNA破坏剂引起的病变中的相对作用。我们的实验结果共同表明，酵母细胞优先利用相对无错的TLS聚合酶绕过给定的病变，并且诱变的TLS聚合酶可以作为备用。有趣的是，如果Polη在某些情况下无法充当TLS聚合酶，则它可能具有反活性。TLS聚合酶之间的合作可能会在生存和压力诱导的诱变之间取得平衡。这些观察结果表明，专门的Y家族DNA聚合酶已经进化为应对不同类型的环境遗传毒性胁迫。