TRAIP regulates replication fork recovery and progression via PCNA
- Cell Discov. 2016 Jun 28;2:16016. doi: 10.1038/celldisc.2016.16.
- 1. School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., China; Centre for Cancer Research, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., China.
- 2. School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., China.
- 3. Life Sciences Institute, Zhejiang University, Zhejiang, China.
- 4. College of Life Sciences, South China Agricultural University, Guangzhou, China.
- 5. School of Life Sciences, University of Science of Technology of China , Hefei, China.
- 6. School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., China; Centre for Cancer Research, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., China.
PCNA is a central scaffold that coordinately assembles replication and repair machineries at DNA replication forks for faithful genome duplication. Here, we describe TRAIP (RNF206) as a novel PCNA-interacting factor that has important roles during mammalian replicative stress responses. We show that TRAIP encodes a nucleolar protein that migrates to stalled replication forks, and that this is accomplished by its targeting of PCNA via an evolutionarily conserved PIP box on its C terminus. Accordingly, inactivation of TRAIP or its interaction with the PCNA clamp compromised replication fork recovery and progression, and leads to chromosome instability. Together, our findings establish TRAIP as a component of the mammalian replicative stress response network, and implicate the TRAIP-PCNA axis in recovery of stalled replication forks.