Error-prone, stress-induced 3′ flap–based Okazaki fragment maturation supports cell survival
Haitao Sun, Zhao‐Ning Lu, Amanpreet Singh, Yajing Zhou, Eric Zheng, Mian Zhou, Jinhui Wang, Xiwei Wu, Zunsong Hu, Zhaohui Gu, Judith L. Campbell, Li Zheng, Binghui Shen
Abstract
Maturation for survival Although cells with defects in DNA replication usually die under stress conditions, some cells acquire new mutations and survive. Sun et al . identified an error-prone, stress-induced Okazaki fragment maturation pathway that induces tandem duplications and enables the survival of cells that have defects in removing the 5′ RNA-DNA flap during DNA replication. In these cells, stress conditions activate DUN1 signaling and induce conversion of the 5′ flap to a 3′ flap that can form secondary structures and be extended and ligated to the downstream DNA fragment, generating alternative duplication mutations similar to the ones in human cancers. The revealed information is analogous to the mechanism in cancer cell evolution and drug resistance. —DJ