How cells with DNA replication defects acquire mutations that allow them to escape apoptosis under environmental stress is a long-standing question. Here, we report that an error-prone Okazaki fragment maturation (OFM) pathway is activated at restrictive temperatures in rad27Δ yeast cells. Restrictive temperature stress activated Dun1, facilitating transformation of unprocessed 5′ flaps into 3′ flaps, which were removed by 3′ nucleases, including DNA polymerase δ (Polδ). However, at certain regions, 3′ flaps formed secondary structures that facilitated 3′ end extension rather than degradation, producing alternative duplications with short spacer sequences, such as pol3 internal tandem duplications. Consequently, little 5′ flap was formed, suppressing rad27Δ-induced lethality at restrictive temperatures. We define a stress-induced, error-prone OFM pathway that generates mutations that counteract replication defects and drive cellular evolution and survival.

中文翻译：

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容易出错、压力诱导的基于 3' 皮瓣的 Okazaki 片段成熟支持细胞存活

具有 DNA 复制缺陷的细胞如何获得突变以使其在环境压力下逃脱细胞凋亡是一个长期存在的问题。在这里，我们报告了一个容易出错的冈崎片段成熟 (OFM) 途径在rad27 Δ 酵母细胞的限制温度下被激活。限制性温度胁迫激活了 Dun1，促进未加工的 5' 皮瓣转化为 3' 皮瓣，这些皮瓣被 3' 核酸酶去除，包括 DNA 聚合酶 δ (Polδ)。然而，在某些区域，3' 瓣形成二级结构，促进 3' 末端延伸而不是降解，产生具有短间隔序列的替代重复，例如pol3内部串联重复。因此，形成了小的 5' 瓣，抑制了 rad27在限制温度下 Δ 诱导的杀伤力。我们定义了一种压力诱导、容易出错的 OFM 途径，该途径产生抵消复制缺陷并驱动细胞进化和存活的突变。