1. Academic Validation
  2. TRAIP regulates replication fork recovery and progression via PCNA

TRAIP regulates replication fork recovery and progression via PCNA

  • Cell Discov. 2016 Jun 28;2:16016. doi: 10.1038/celldisc.2016.16.
Wanjuan Feng 1 Yingying Guo 2 Jun Huang 3 Yiqun Deng 4 Jianye Zang 5 Michael Shing-Yan Huen 6
Affiliations

Affiliations

  • 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.
Abstract

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.

Keywords

DNA damage; PCNA; RNF206; TRAIP; hydroxyurea; replication.

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