Molecular Cell
06 February 2025
DDX39A resolves replication fork-associated RNA-DNA hybrids to balance fork protection and cleavage for genomic stability maintenance
Zhanzhan Xu,1,4 Chen Nie,1,4 Junwei Liao,1 Yujie Ma,1 Xiao Albert Zhou,1 Xiaoman Li,1 Shiwei Li,1 Haodong Lin,1 Yefei Luo,1 Kaiqi Cheng,1 Zuchao Mao,1 Lei Zhang,1 Yichen Pan,1 Yuke Chen,2 Weibin Wang1,* and Jiadong Wang1,3,5,*
1 Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China
2 Department of Urology, Peking University First Hospital, Beijing 100034, China
3 Department of Gastrointestinal Translational Research, Peking University Cancer Hospital, Beijing 100142, China
4 These authors contributed equally
5 Lead contact
10.1016/j.molcel.2024.11.029
Replication fork-associated RNA-DNA hybrids (RF-RDs), symbolized by a chrysalis, protect DNA replication forks (butterflies) from degradation in transcriptionally active regions. The resolution of RF-RDs by DDX39A, depicted as the chrysalis opening, facilitates DNA2-mediated resection and replication restart, enabling the butterfly to fly. In this issue of Molecular Cell, Xu et al. show that RF-RDs protect replication forks, and their resolution by DDX39A promotes DNA2-mediated resection and replication restart.
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