研究人员发现，在rad27Δ酵母细胞的限制性温度下，易出错的冈崎片段成熟（OFM）途径被激活。限制性温度压力激活了Dun1，促进了未加工的5′flap转化为3′flap，这被3′核酸酶去除，包括DNA聚合酶δ（Polδ）。然而，在某些区域，3′flap形成二级结构，有利于3′端延伸而不是降解，从而产生具有短间隔序列的替代性复制，如pol3内部串联复制。因此，很少形成5′flap，从而抑制了rad27Δ在限制性温度下诱导的致死性。
研究人员定义了一个压力诱导的、容易出错的OFM途径，它产生的突变可以抵消复制缺陷，并驱动细胞进化和生存。
据了解，具有DNA复制缺陷的细胞如何获得突变，使其在环境压力下逃脱凋亡是一个长期存在的问题。
附：英文原文
Title: Error-prone, stress-induced 3′ flap–based Okazaki fragment maturation supports cell survival
Author: Haitao Sun, Zhaoning Lu, Amanpreet Singh, Yajing Zhou, Eric Zheng, Mian Zhou, Jinhui Wang, Xiwei Wu, Zunsong Hu, Zhaohui Gu, Judith L. Campbell, Li Zheng, Binghui Shen
Issue&Volume: 2021-12-03
Abstract: 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.
DOI: abj1013
Source: https://www.science.org/doi/10.1126/science.abj1013